La maladie de Parkinson en France (serveur d'exploration)

Attention, ce site est en cours de développement !
Attention, site généré par des moyens informatiques à partir de corpus bruts.
Les informations ne sont donc pas validées.

Behavioral Phenotyping of Parkin-Deficient Mice: Looking for Early Preclinical Features of Parkinson's Disease

Identifieur interne : 000094 ( Pmc/Curation ); précédent : 000093; suivant : 000095

Behavioral Phenotyping of Parkin-Deficient Mice: Looking for Early Preclinical Features of Parkinson's Disease

Auteurs : Daniel Rial [Brésil, Portugal] ; Adalberto A. Castro [Brésil] ; Nuno Machado [Portugal] ; Pedro Garção [Portugal] ; Francisco Q. Gonçalves [Portugal] ; Henrique B. Silva [Portugal] ; Ângelo R. Tomé [Portugal] ; Attila Köfalvi [Portugal] ; Olga Corti [France] ; Rita Raisman-Vozari [France] ; Rodrigo A. Cunha [Portugal] ; Rui D. Prediger [Brésil]

Source :

RBID : PMC:4259468

Abstract

There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson's disease (PD) begin many years before the appearance of the characteristic motor symptoms. Neuropsychiatric, sensorial and cognitive deficits are recognized as early non-motor manifestations of PD, and are not attenuated by the current anti-parkinsonian therapy. Although loss-of-function mutations in the parkin gene cause early-onset familial PD, Parkin-deficient mice do not display spontaneous degeneration of the nigrostriatal pathway or enhanced vulnerability to dopaminergic neurotoxins such as 6-OHDA and MPTP. Here, we employed adult homozygous C57BL/6 mice with parkin gene deletion on exon 3 (parkin−/−) to further investigate the relevance of Parkin in the regulation of non-motor features, namely olfactory, emotional, cognitive and hippocampal synaptic plasticity. Parkin−/− mice displayed normal performance on behavioral tests evaluating olfaction (olfactory discrimination), anxiety (elevated plus-maze), depressive-like behavior (forced swimming and tail suspension) and motor function (rotarod, grasping strength and pole). However, parkin−/− mice displayed a poor performance in the open field habituation, object location and modified Y-maze tasks suggestive of procedural and short-term spatial memory deficits. These behavioral impairments were accompanied by impaired hippocampal long-term potentiation (LTP). These findings indicate that the genetic deletion of parkin causes deficiencies in hippocampal synaptic plasticity, resulting in memory deficits with no major olfactory, emotional or motor impairments. Therefore, parkin−/− mice may represent a promising animal model to study the early stages of PD and for testing new therapeutic strategies to restore learning and memory and synaptic plasticity impairments in PD.


Url:
DOI: 10.1371/journal.pone.0114216
PubMed: 25486126
PubMed Central: 4259468

Links toward previous steps (curation, corpus...)


Links to Exploration step

PMC:4259468

Le document en format XML

<record>
<TEI>
<teiHeader>
<fileDesc>
<titleStmt>
<title xml:lang="en">Behavioral Phenotyping of Parkin-Deficient Mice: Looking for Early Preclinical Features of Parkinson's Disease</title>
<author>
<name sortKey="Rial, Daniel" sort="Rial, Daniel" uniqKey="Rial D" first="Daniel" last="Rial">Daniel Rial</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<addr-line>Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, 88049-900, SC, Brazil</addr-line>
</nlm:aff>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, 88049-900, SC</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Castro, Adalberto A" sort="Castro, Adalberto A" uniqKey="Castro A" first="Adalberto A." last="Castro">Adalberto A. Castro</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<addr-line>Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, 88049-900, SC, Brazil</addr-line>
</nlm:aff>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, 88049-900, SC</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Machado, Nuno" sort="Machado, Nuno" uniqKey="Machado N" first="Nuno" last="Machado">Nuno Machado</name>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Garcao, Pedro" sort="Garcao, Pedro" uniqKey="Garcao P" first="Pedro" last="Garção">Pedro Garção</name>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Goncalves, Francisco Q" sort="Goncalves, Francisco Q" uniqKey="Goncalves F" first="Francisco Q." last="Gonçalves">Francisco Q. Gonçalves</name>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Silva, Henrique B" sort="Silva, Henrique B" uniqKey="Silva H" first="Henrique B." last="Silva">Henrique B. Silva</name>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Tome, Angelo R" sort="Tome, Angelo R" uniqKey="Tome A" first="Ângelo R." last="Tomé">Ângelo R. Tomé</name>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<addr-line>Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000-456, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000-456, Coimbra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Kofalvi, Attila" sort="Kofalvi, Attila" uniqKey="Kofalvi A" first="Attila" last="Köfalvi">Attila Köfalvi</name>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Corti, Olga" sort="Corti, Olga" uniqKey="Corti O" first="Olga" last="Corti">Olga Corti</name>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<addr-line>CNRS UMR 7225, Hôpital de la Salpêtrière—Bâtiment, ICM (Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière), CRICM, Thérapeutique Expérimentale de la Neurodégénérescence, Université Pierre et Marie Curie, UPMC, 75651, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS UMR 7225, Hôpital de la Salpêtrière—Bâtiment, ICM (Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière), CRICM, Thérapeutique Expérimentale de la Neurodégénérescence, Université Pierre et Marie Curie, UPMC, 75651, Paris</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Raisman Vozari, Rita" sort="Raisman Vozari, Rita" uniqKey="Raisman Vozari R" first="Rita" last="Raisman-Vozari">Rita Raisman-Vozari</name>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<addr-line>CNRS UMR 7225, Hôpital de la Salpêtrière—Bâtiment, ICM (Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière), CRICM, Thérapeutique Expérimentale de la Neurodégénérescence, Université Pierre et Marie Curie, UPMC, 75651, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS UMR 7225, Hôpital de la Salpêtrière—Bâtiment, ICM (Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière), CRICM, Thérapeutique Expérimentale de la Neurodégénérescence, Université Pierre et Marie Curie, UPMC, 75651, Paris</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Cunha, Rodrigo A" sort="Cunha, Rodrigo A" uniqKey="Cunha R" first="Rodrigo A." last="Cunha">Rodrigo A. Cunha</name>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff5">
<addr-line>Faculty of Medicine, University of Coimbra, 3005-504, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>Faculty of Medicine, University of Coimbra, 3005-504, Coimbra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Prediger, Rui D" sort="Prediger, Rui D" uniqKey="Prediger R" first="Rui D." last="Prediger">Rui D. Prediger</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<addr-line>Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, 88049-900, SC, Brazil</addr-line>
</nlm:aff>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, 88049-900, SC</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt>
<idno type="wicri:source">PMC</idno>
<idno type="pmid">25486126</idno>
<idno type="pmc">4259468</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259468</idno>
<idno type="RBID">PMC:4259468</idno>
<idno type="doi">10.1371/journal.pone.0114216</idno>
<date when="2014">2014</date>
<idno type="wicri:Area/Pmc/Corpus">000094</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000094</idno>
<idno type="wicri:Area/Pmc/Curation">000094</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000094</idno>
</publicationStmt>
<sourceDesc>
<biblStruct>
<analytic>
<title xml:lang="en" level="a" type="main">Behavioral Phenotyping of Parkin-Deficient Mice: Looking for Early Preclinical Features of Parkinson's Disease</title>
<author>
<name sortKey="Rial, Daniel" sort="Rial, Daniel" uniqKey="Rial D" first="Daniel" last="Rial">Daniel Rial</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<addr-line>Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, 88049-900, SC, Brazil</addr-line>
</nlm:aff>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, 88049-900, SC</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Castro, Adalberto A" sort="Castro, Adalberto A" uniqKey="Castro A" first="Adalberto A." last="Castro">Adalberto A. Castro</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<addr-line>Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, 88049-900, SC, Brazil</addr-line>
</nlm:aff>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, 88049-900, SC</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Machado, Nuno" sort="Machado, Nuno" uniqKey="Machado N" first="Nuno" last="Machado">Nuno Machado</name>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Garcao, Pedro" sort="Garcao, Pedro" uniqKey="Garcao P" first="Pedro" last="Garção">Pedro Garção</name>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Goncalves, Francisco Q" sort="Goncalves, Francisco Q" uniqKey="Goncalves F" first="Francisco Q." last="Gonçalves">Francisco Q. Gonçalves</name>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Silva, Henrique B" sort="Silva, Henrique B" uniqKey="Silva H" first="Henrique B." last="Silva">Henrique B. Silva</name>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Tome, Angelo R" sort="Tome, Angelo R" uniqKey="Tome A" first="Ângelo R." last="Tomé">Ângelo R. Tomé</name>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<addr-line>Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000-456, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000-456, Coimbra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Kofalvi, Attila" sort="Kofalvi, Attila" uniqKey="Kofalvi A" first="Attila" last="Köfalvi">Attila Köfalvi</name>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Corti, Olga" sort="Corti, Olga" uniqKey="Corti O" first="Olga" last="Corti">Olga Corti</name>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<addr-line>CNRS UMR 7225, Hôpital de la Salpêtrière—Bâtiment, ICM (Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière), CRICM, Thérapeutique Expérimentale de la Neurodégénérescence, Université Pierre et Marie Curie, UPMC, 75651, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS UMR 7225, Hôpital de la Salpêtrière—Bâtiment, ICM (Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière), CRICM, Thérapeutique Expérimentale de la Neurodégénérescence, Université Pierre et Marie Curie, UPMC, 75651, Paris</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Raisman Vozari, Rita" sort="Raisman Vozari, Rita" uniqKey="Raisman Vozari R" first="Rita" last="Raisman-Vozari">Rita Raisman-Vozari</name>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<addr-line>CNRS UMR 7225, Hôpital de la Salpêtrière—Bâtiment, ICM (Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière), CRICM, Thérapeutique Expérimentale de la Neurodégénérescence, Université Pierre et Marie Curie, UPMC, 75651, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS UMR 7225, Hôpital de la Salpêtrière—Bâtiment, ICM (Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière), CRICM, Thérapeutique Expérimentale de la Neurodégénérescence, Université Pierre et Marie Curie, UPMC, 75651, Paris</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Cunha, Rodrigo A" sort="Cunha, Rodrigo A" uniqKey="Cunha R" first="Rodrigo A." last="Cunha">Rodrigo A. Cunha</name>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff5">
<addr-line>Faculty of Medicine, University of Coimbra, 3005-504, Coimbra, Portugal</addr-line>
</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>Faculty of Medicine, University of Coimbra, 3005-504, Coimbra</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Prediger, Rui D" sort="Prediger, Rui D" uniqKey="Prediger R" first="Rui D." last="Prediger">Rui D. Prediger</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<addr-line>Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, 88049-900, SC, Brazil</addr-line>
</nlm:aff>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, 88049-900, SC</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint>
<date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson's disease (PD) begin many years before the appearance of the characteristic motor symptoms. Neuropsychiatric, sensorial and cognitive deficits are recognized as early non-motor manifestations of PD, and are not attenuated by the current anti-parkinsonian therapy. Although loss-of-function mutations in the
<italic>parkin</italic>
gene cause early-onset familial PD, Parkin-deficient mice do not display spontaneous degeneration of the nigrostriatal pathway or enhanced vulnerability to dopaminergic neurotoxins such as 6-OHDA and MPTP. Here, we employed adult homozygous C57BL/6 mice with
<italic>parkin</italic>
gene deletion on exon 3 (
<italic>parkin</italic>
<sup>−/−</sup>
) to further investigate the relevance of Parkin in the regulation of non-motor features, namely olfactory, emotional, cognitive and hippocampal synaptic plasticity.
<italic>Parkin</italic>
<sup>−/−</sup>
mice displayed normal performance on behavioral tests evaluating olfaction (olfactory discrimination), anxiety (elevated plus-maze), depressive-like behavior (forced swimming and tail suspension) and motor function (rotarod, grasping strength and pole). However,
<italic>parkin</italic>
<sup>−/−</sup>
mice displayed a poor performance in the open field habituation, object location and modified Y-maze tasks suggestive of procedural and short-term spatial memory deficits. These behavioral impairments were accompanied by impaired hippocampal long-term potentiation (LTP). These findings indicate that the genetic deletion of
<italic>parkin</italic>
causes deficiencies in hippocampal synaptic plasticity, resulting in memory deficits with no major olfactory, emotional or motor impairments. Therefore,
<italic>parkin</italic>
<sup>−/−</sup>
mice may represent a promising animal model to study the early stages of PD and for testing new therapeutic strategies to restore learning and memory and synaptic plasticity impairments in PD.</p>
</div>
</front>
<back>
<div1 type="bibliography">
<listBibl>
<biblStruct>
<analytic>
<author>
<name sortKey="De Lau, Lm" uniqKey="De Lau L">LM de Lau</name>
</author>
<author>
<name sortKey="Koudstaal, Pj" uniqKey="Koudstaal P">PJ Koudstaal</name>
</author>
<author>
<name sortKey="Hofman, A" uniqKey="Hofman A">A Hofman</name>
</author>
<author>
<name sortKey="Breteler, Mm" uniqKey="Breteler M">MM Breteler</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Hirsch, E" uniqKey="Hirsch E">E Hirsch</name>
</author>
<author>
<name sortKey="Graybiel, Am" uniqKey="Graybiel A">AM Graybiel</name>
</author>
<author>
<name sortKey="Agid, Ya" uniqKey="Agid Y">YA Agid</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Braak, H" uniqKey="Braak H">H Braak</name>
</author>
<author>
<name sortKey="Ghebremedhin, E" uniqKey="Ghebremedhin E">E Ghebremedhin</name>
</author>
<author>
<name sortKey="Rub, U" uniqKey="Rub U">U Rub</name>
</author>
<author>
<name sortKey="Bratzke, H" uniqKey="Bratzke H">H Bratzke</name>
</author>
<author>
<name sortKey="Del Tredici, K" uniqKey="Del Tredici K">K Del Tredici</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Chaudhuri, Kr" uniqKey="Chaudhuri K">KR Chaudhuri</name>
</author>
<author>
<name sortKey="Odin, P" uniqKey="Odin P">P Odin</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Pinna, A" uniqKey="Pinna A">A Pinna</name>
</author>
<author>
<name sortKey="Morelli, M" uniqKey="Morelli M">M Morelli</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Taylor, Tn" uniqKey="Taylor T">TN Taylor</name>
</author>
<author>
<name sortKey="Greene, Jg" uniqKey="Greene J">JG Greene</name>
</author>
<author>
<name sortKey="Miller, Gw" uniqKey="Miller G">GW Miller</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Doty, Rl" uniqKey="Doty R">RL Doty</name>
</author>
<author>
<name sortKey="Deems, Da" uniqKey="Deems D">DA Deems</name>
</author>
<author>
<name sortKey="Stellar, S" uniqKey="Stellar S">S Stellar</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Muller, A" uniqKey="Muller A">A Muller</name>
</author>
<author>
<name sortKey="Mungersdorf, M" uniqKey="Mungersdorf M">M Mungersdorf</name>
</author>
<author>
<name sortKey="Reichmann, H" uniqKey="Reichmann H">H Reichmann</name>
</author>
<author>
<name sortKey="Strehle, G" uniqKey="Strehle G">G Strehle</name>
</author>
<author>
<name sortKey="Hummel, T" uniqKey="Hummel T">T Hummel</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Prediger, Rd" uniqKey="Prediger R">RD Prediger</name>
</author>
<author>
<name sortKey="Matheus, Fc" uniqKey="Matheus F">FC Matheus</name>
</author>
<author>
<name sortKey="Schwarzbold, Ml" uniqKey="Schwarzbold M">ML Schwarzbold</name>
</author>
<author>
<name sortKey="Lima, Mm" uniqKey="Lima M">MM Lima</name>
</author>
<author>
<name sortKey="Vital, Ma" uniqKey="Vital M">MA Vital</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Tolosa, E" uniqKey="Tolosa E">E Tolosa</name>
</author>
<author>
<name sortKey="Compta, Y" uniqKey="Compta Y">Y Compta</name>
</author>
<author>
<name sortKey="Gaig, C" uniqKey="Gaig C">C Gaig</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Dubois, B" uniqKey="Dubois B">B Dubois</name>
</author>
<author>
<name sortKey="Pillon, B" uniqKey="Pillon B">B Pillon</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Stebbins, Gt" uniqKey="Stebbins G">GT Stebbins</name>
</author>
<author>
<name sortKey="Gabrieli, Jd" uniqKey="Gabrieli J">JD Gabrieli</name>
</author>
<author>
<name sortKey="Masciari, F" uniqKey="Masciari F">F Masciari</name>
</author>
<author>
<name sortKey="Monti, L" uniqKey="Monti L">L Monti</name>
</author>
<author>
<name sortKey="Goetz, Cg" uniqKey="Goetz C">CG Goetz</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Lewis, Sj" uniqKey="Lewis S">SJ Lewis</name>
</author>
<author>
<name sortKey="Dove, A" uniqKey="Dove A">A Dove</name>
</author>
<author>
<name sortKey="Robbins, Tw" uniqKey="Robbins T">TW Robbins</name>
</author>
<author>
<name sortKey="Barker, Ra" uniqKey="Barker R">RA Barker</name>
</author>
<author>
<name sortKey="Owen, Am" uniqKey="Owen A">AM Owen</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Da Cunha, C" uniqKey="Da Cunha C">C Da Cunha</name>
</author>
<author>
<name sortKey="Angelucci, Me" uniqKey="Angelucci M">ME Angelucci</name>
</author>
<author>
<name sortKey="Canteras, Ns" uniqKey="Canteras N">NS Canteras</name>
</author>
<author>
<name sortKey="Wonnacott, S" uniqKey="Wonnacott S">S Wonnacott</name>
</author>
<author>
<name sortKey="Takahashi, Rn" uniqKey="Takahashi R">RN Takahashi</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Prediger, Rd" uniqKey="Prediger R">RD Prediger</name>
</author>
<author>
<name sortKey="Aguiar, As" uniqKey="Aguiar A">AS Aguiar</name>
</author>
<author>
<name sortKey="Rojas Mayorquin, Ae" uniqKey="Rojas Mayorquin A">AE Rojas-Mayorquin</name>
</author>
<author>
<name sortKey="Figueiredo, Cp" uniqKey="Figueiredo C">CP Figueiredo</name>
</author>
<author>
<name sortKey="Matheus, Fc" uniqKey="Matheus F">FC Matheus</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Prediger, Rd" uniqKey="Prediger R">RD Prediger</name>
</author>
<author>
<name sortKey="Rojas Mayorquin, Ae" uniqKey="Rojas Mayorquin A">AE Rojas-Mayorquin</name>
</author>
<author>
<name sortKey="Aguiar, As" uniqKey="Aguiar A">AS Aguiar</name>
</author>
<author>
<name sortKey="Chevarin, C" uniqKey="Chevarin C">C Chevarin</name>
</author>
<author>
<name sortKey="Mongeau, R" uniqKey="Mongeau R">R Mongeau</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Moreira, El" uniqKey="Moreira E">EL Moreira</name>
</author>
<author>
<name sortKey="Rial, D" uniqKey="Rial D">D Rial</name>
</author>
<author>
<name sortKey="Aguiar, As" uniqKey="Aguiar A">AS Aguiar</name>
</author>
<author>
<name sortKey="Figueiredo, Cp" uniqKey="Figueiredo C">CP Figueiredo</name>
</author>
<author>
<name sortKey="Siqueira, Jm" uniqKey="Siqueira J">JM Siqueira</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Dawson, Tm" uniqKey="Dawson T">TM Dawson</name>
</author>
<author>
<name sortKey="Ko, Hs" uniqKey="Ko H">HS Ko</name>
</author>
<author>
<name sortKey="Dawson, Vl" uniqKey="Dawson V">VL Dawson</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Kitada, T" uniqKey="Kitada T">T Kitada</name>
</author>
<author>
<name sortKey="Asakawa, S" uniqKey="Asakawa S">S Asakawa</name>
</author>
<author>
<name sortKey="Hattori, N" uniqKey="Hattori N">N Hattori</name>
</author>
<author>
<name sortKey="Matsumine, H" uniqKey="Matsumine H">H Matsumine</name>
</author>
<author>
<name sortKey="Yamamura, Y" uniqKey="Yamamura Y">Y Yamamura</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Lucking, Cb" uniqKey="Lucking C">CB Lucking</name>
</author>
<author>
<name sortKey="Durr, A" uniqKey="Durr A">A Durr</name>
</author>
<author>
<name sortKey="Bonifati, V" uniqKey="Bonifati V">V Bonifati</name>
</author>
<author>
<name sortKey="Vaughan, J" uniqKey="Vaughan J">J Vaughan</name>
</author>
<author>
<name sortKey="De Michele, G" uniqKey="De Michele G">G De Michele</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Shimura, H" uniqKey="Shimura H">H Shimura</name>
</author>
<author>
<name sortKey="Hattori, N" uniqKey="Hattori N">N Hattori</name>
</author>
<author>
<name sortKey="Kubo, S" uniqKey="Kubo S">S Kubo</name>
</author>
<author>
<name sortKey="Mizuno, Y" uniqKey="Mizuno Y">Y Mizuno</name>
</author>
<author>
<name sortKey="Asakawa, S" uniqKey="Asakawa S">S Asakawa</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Kahle, Pj" uniqKey="Kahle P">PJ Kahle</name>
</author>
<author>
<name sortKey="Haass, C" uniqKey="Haass C">C Haass</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Chung, Kk" uniqKey="Chung K">KK Chung</name>
</author>
<author>
<name sortKey="Thomas, B" uniqKey="Thomas B">B Thomas</name>
</author>
<author>
<name sortKey="Li, X" uniqKey="Li X">X Li</name>
</author>
<author>
<name sortKey="Pletnikova, O" uniqKey="Pletnikova O">O Pletnikova</name>
</author>
<author>
<name sortKey="Troncoso, Jc" uniqKey="Troncoso J">JC Troncoso</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Lavoie, Mj" uniqKey="Lavoie M">MJ LaVoie</name>
</author>
<author>
<name sortKey="Ostaszewski, Bl" uniqKey="Ostaszewski B">BL Ostaszewski</name>
</author>
<author>
<name sortKey="Weihofen, A" uniqKey="Weihofen A">A Weihofen</name>
</author>
<author>
<name sortKey="Schlossmacher, Mg" uniqKey="Schlossmacher M">MG Schlossmacher</name>
</author>
<author>
<name sortKey="Selkoe, Dj" uniqKey="Selkoe D">DJ Selkoe</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Palacino, Jj" uniqKey="Palacino J">JJ Palacino</name>
</author>
<author>
<name sortKey="Sagi, D" uniqKey="Sagi D">D Sagi</name>
</author>
<author>
<name sortKey="Goldberg, Ms" uniqKey="Goldberg M">MS Goldberg</name>
</author>
<author>
<name sortKey="Krauss, S" uniqKey="Krauss S">S Krauss</name>
</author>
<author>
<name sortKey="Motz, C" uniqKey="Motz C">C Motz</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Itier, Jm" uniqKey="Itier J">JM Itier</name>
</author>
<author>
<name sortKey="Ibanez, P" uniqKey="Ibanez P">P Ibanez</name>
</author>
<author>
<name sortKey="Mena, Ma" uniqKey="Mena M">MA Mena</name>
</author>
<author>
<name sortKey="Abbas, N" uniqKey="Abbas N">N Abbas</name>
</author>
<author>
<name sortKey="Cohen Salmon, C" uniqKey="Cohen Salmon C">C Cohen-Salmon</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Darios, F" uniqKey="Darios F">F Darios</name>
</author>
<author>
<name sortKey="Corti, O" uniqKey="Corti O">O Corti</name>
</author>
<author>
<name sortKey="Lucking, Cb" uniqKey="Lucking C">CB Lucking</name>
</author>
<author>
<name sortKey="Hampe, C" uniqKey="Hampe C">C Hampe</name>
</author>
<author>
<name sortKey="Muriel, Mp" uniqKey="Muriel M">MP Muriel</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Haque, Me" uniqKey="Haque M">ME Haque</name>
</author>
<author>
<name sortKey="Mount, Mp" uniqKey="Mount M">MP Mount</name>
</author>
<author>
<name sortKey="Safarpour, F" uniqKey="Safarpour F">F Safarpour</name>
</author>
<author>
<name sortKey="Abdel Messih, E" uniqKey="Abdel Messih E">E Abdel-Messih</name>
</author>
<author>
<name sortKey="Callaghan, S" uniqKey="Callaghan S">S Callaghan</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Yasuda, T" uniqKey="Yasuda T">T Yasuda</name>
</author>
<author>
<name sortKey="Hayakawa, H" uniqKey="Hayakawa H">H Hayakawa</name>
</author>
<author>
<name sortKey="Nihira, T" uniqKey="Nihira T">T Nihira</name>
</author>
<author>
<name sortKey="Ren, Yr" uniqKey="Ren Y">YR Ren</name>
</author>
<author>
<name sortKey="Nakata, Y" uniqKey="Nakata Y">Y Nakata</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Aguiar, As" uniqKey="Aguiar A">AS Aguiar</name>
</author>
<author>
<name sortKey="Tristao, Fs" uniqKey="Tristao F">FS Tristao</name>
</author>
<author>
<name sortKey="Amar, M" uniqKey="Amar M">M Amar</name>
</author>
<author>
<name sortKey="Chevarin, C" uniqKey="Chevarin C">C Chevarin</name>
</author>
<author>
<name sortKey="Lanfumey, L" uniqKey="Lanfumey L">L Lanfumey</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Zhu, Xr" uniqKey="Zhu X">XR Zhu</name>
</author>
<author>
<name sortKey="Maskri, L" uniqKey="Maskri L">L Maskri</name>
</author>
<author>
<name sortKey="Herold, C" uniqKey="Herold C">C Herold</name>
</author>
<author>
<name sortKey="Bader, V" uniqKey="Bader V">V Bader</name>
</author>
<author>
<name sortKey="Stichel, Cc" uniqKey="Stichel C">CC Stichel</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Kurtenbach, S" uniqKey="Kurtenbach S">S Kurtenbach</name>
</author>
<author>
<name sortKey="Wewering, S" uniqKey="Wewering S">S Wewering</name>
</author>
<author>
<name sortKey="Hatt, H" uniqKey="Hatt H">H Hatt</name>
</author>
<author>
<name sortKey="Neuhaus, Em" uniqKey="Neuhaus E">EM Neuhaus</name>
</author>
<author>
<name sortKey="Lubbert, H" uniqKey="Lubbert H">H Lubbert</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Lister, Rg" uniqKey="Lister R">RG Lister</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Steru, L" uniqKey="Steru L">L Steru</name>
</author>
<author>
<name sortKey="Chermat, R" uniqKey="Chermat R">R Chermat</name>
</author>
<author>
<name sortKey="Thierry, B" uniqKey="Thierry B">B Thierry</name>
</author>
<author>
<name sortKey="Simon, P" uniqKey="Simon P">P Simon</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Porsolt, Rd" uniqKey="Porsolt R">RD Porsolt</name>
</author>
<author>
<name sortKey="Bertin, A" uniqKey="Bertin A">A Bertin</name>
</author>
<author>
<name sortKey="Jalfre, M" uniqKey="Jalfre M">M Jalfre</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Vieira, C" uniqKey="Vieira C">C Vieira</name>
</author>
<author>
<name sortKey="De Lima, Tc" uniqKey="De Lima T">TC De Lima</name>
</author>
<author>
<name sortKey="Carobrez Ade, P" uniqKey="Carobrez Ade P">P Carobrez Ade</name>
</author>
<author>
<name sortKey="Lino De Oliveira, C" uniqKey="Lino De Oliveira C">C Lino-de-Oliveira</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Kheirbek, Ma" uniqKey="Kheirbek M">MA Kheirbek</name>
</author>
<author>
<name sortKey="Britt, Jp" uniqKey="Britt J">JP Britt</name>
</author>
<author>
<name sortKey="Beeler, Ja" uniqKey="Beeler J">JA Beeler</name>
</author>
<author>
<name sortKey="Ishikawa, Y" uniqKey="Ishikawa Y">Y Ishikawa</name>
</author>
<author>
<name sortKey="Mcgehee, Ds" uniqKey="Mcgehee D">DS McGehee</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Bertelli, Ja" uniqKey="Bertelli J">JA Bertelli</name>
</author>
<author>
<name sortKey="Mira, Jc" uniqKey="Mira J">JC Mira</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Fleming, Sm" uniqKey="Fleming S">SM Fleming</name>
</author>
<author>
<name sortKey="Salcedo, J" uniqKey="Salcedo J">J Salcedo</name>
</author>
<author>
<name sortKey="Fernagut, Po" uniqKey="Fernagut P">PO Fernagut</name>
</author>
<author>
<name sortKey="Rockenstein, E" uniqKey="Rockenstein E">E Rockenstein</name>
</author>
<author>
<name sortKey="Masliah, E" uniqKey="Masliah E">E Masliah</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Walker, Jm" uniqKey="Walker J">JM Walker</name>
</author>
<author>
<name sortKey="Fowler, Sw" uniqKey="Fowler S">SW Fowler</name>
</author>
<author>
<name sortKey="Miller, Dk" uniqKey="Miller D">DK Miller</name>
</author>
<author>
<name sortKey="Sun, Ay" uniqKey="Sun A">AY Sun</name>
</author>
<author>
<name sortKey="Weisman, Ga" uniqKey="Weisman G">GA Weisman</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Assini, Fl" uniqKey="Assini F">FL Assini</name>
</author>
<author>
<name sortKey="Duzzioni, M" uniqKey="Duzzioni M">M Duzzioni</name>
</author>
<author>
<name sortKey="Takahashi, Rn" uniqKey="Takahashi R">RN Takahashi</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Moreira, El" uniqKey="Moreira E">EL Moreira</name>
</author>
<author>
<name sortKey="De Oliveira, J" uniqKey="De Oliveira J">J de Oliveira</name>
</author>
<author>
<name sortKey="Nunes, Jc" uniqKey="Nunes J">JC Nunes</name>
</author>
<author>
<name sortKey="Santos, Db" uniqKey="Santos D">DB Santos</name>
</author>
<author>
<name sortKey="Nunes, Fc" uniqKey="Nunes F">FC Nunes</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Soares, E" uniqKey="Soares E">E Soares</name>
</author>
<author>
<name sortKey="Prediger, Rd" uniqKey="Prediger R">RD Prediger</name>
</author>
<author>
<name sortKey="Nunes, S" uniqKey="Nunes S">S Nunes</name>
</author>
<author>
<name sortKey="Castro, Aa" uniqKey="Castro A">AA Castro</name>
</author>
<author>
<name sortKey="Viana, Sd" uniqKey="Viana S">SD Viana</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Anderson, Ww" uniqKey="Anderson W">WW Anderson</name>
</author>
<author>
<name sortKey="Collingridge, Gl" uniqKey="Collingridge G">GL Collingridge</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Diogenes, Mj" uniqKey="Diogenes M">MJ Diogenes</name>
</author>
<author>
<name sortKey="Fernandes, Cc" uniqKey="Fernandes C">CC Fernandes</name>
</author>
<author>
<name sortKey="Sebastiao, Am" uniqKey="Sebastiao A">AM Sebastiao</name>
</author>
<author>
<name sortKey="Ribeiro, Ja" uniqKey="Ribeiro J">JA Ribeiro</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Ferreira, Sg" uniqKey="Ferreira S">SG Ferreira</name>
</author>
<author>
<name sortKey="Lomaglio, T" uniqKey="Lomaglio T">T Lomaglio</name>
</author>
<author>
<name sortKey="Avelino, A" uniqKey="Avelino A">A Avelino</name>
</author>
<author>
<name sortKey="Cruz, F" uniqKey="Cruz F">F Cruz</name>
</author>
<author>
<name sortKey="Oliveira, Cr" uniqKey="Oliveira C">CR Oliveira</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Koles, L" uniqKey="Koles L">L Koles</name>
</author>
<author>
<name sortKey="Garcao, P" uniqKey="Garcao P">P Garcao</name>
</author>
<author>
<name sortKey="Zadori, Zs" uniqKey="Zadori Z">ZS Zadori</name>
</author>
<author>
<name sortKey="Ferreira, Sg" uniqKey="Ferreira S">SG Ferreira</name>
</author>
<author>
<name sortKey="Pinheiro, Bs" uniqKey="Pinheiro B">BS Pinheiro</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Whittaker, Vp" uniqKey="Whittaker V">VP Whittaker</name>
</author>
<author>
<name sortKey="Michaelson, Ia" uniqKey="Michaelson I">IA Michaelson</name>
</author>
<author>
<name sortKey="Kirkland, Rj" uniqKey="Kirkland R">RJ Kirkland</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Raiteri, L" uniqKey="Raiteri L">L Raiteri</name>
</author>
<author>
<name sortKey="Raiteri, M" uniqKey="Raiteri M">M Raiteri</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Ferreira, Sg" uniqKey="Ferreira S">SG Ferreira</name>
</author>
<author>
<name sortKey="Teixeira, Fm" uniqKey="Teixeira F">FM Teixeira</name>
</author>
<author>
<name sortKey="Garcao, P" uniqKey="Garcao P">P Garcao</name>
</author>
<author>
<name sortKey="Agostinho, P" uniqKey="Agostinho P">P Agostinho</name>
</author>
<author>
<name sortKey="Ledent, C" uniqKey="Ledent C">C Ledent</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Leussis, Mp" uniqKey="Leussis M">MP Leussis</name>
</author>
<author>
<name sortKey="Bolivar, Vj" uniqKey="Bolivar V">VJ Bolivar</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Anders, S" uniqKey="Anders S">S Anders</name>
</author>
<author>
<name sortKey="Sack, B" uniqKey="Sack B">B Sack</name>
</author>
<author>
<name sortKey="Pohl, A" uniqKey="Pohl A">A Pohl</name>
</author>
<author>
<name sortKey="Munte, T" uniqKey="Munte T">T Munte</name>
</author>
<author>
<name sortKey="Pramstaller, P" uniqKey="Pramstaller P">P Pramstaller</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Dellu, F" uniqKey="Dellu F">F Dellu</name>
</author>
<author>
<name sortKey="Mayo, W" uniqKey="Mayo W">W Mayo</name>
</author>
<author>
<name sortKey="Cherkaoui, J" uniqKey="Cherkaoui J">J Cherkaoui</name>
</author>
<author>
<name sortKey="Le Moal, M" uniqKey="Le Moal M">M Le Moal</name>
</author>
<author>
<name sortKey="Simon, H" uniqKey="Simon H">H Simon</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Dellu, F" uniqKey="Dellu F">F Dellu</name>
</author>
<author>
<name sortKey="Fauchey, V" uniqKey="Fauchey V">V Fauchey</name>
</author>
<author>
<name sortKey="Le Moal, M" uniqKey="Le Moal M">M Le Moal</name>
</author>
<author>
<name sortKey="Simon, H" uniqKey="Simon H">H Simon</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Mclamb, Rl" uniqKey="Mclamb R">RL McLamb</name>
</author>
<author>
<name sortKey="Mundy, Wr" uniqKey="Mundy W">WR Mundy</name>
</author>
<author>
<name sortKey="Tilson, Ha" uniqKey="Tilson H">HA Tilson</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Petit, Gh" uniqKey="Petit G">GH Petit</name>
</author>
<author>
<name sortKey="Tobin, C" uniqKey="Tobin C">C Tobin</name>
</author>
<author>
<name sortKey="Krishnan, K" uniqKey="Krishnan K">K Krishnan</name>
</author>
<author>
<name sortKey="Moricard, Y" uniqKey="Moricard Y">Y Moricard</name>
</author>
<author>
<name sortKey="Covey, Df" uniqKey="Covey D">DF Covey</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Niu, L" uniqKey="Niu L">L Niu</name>
</author>
<author>
<name sortKey="Cao, B" uniqKey="Cao B">B Cao</name>
</author>
<author>
<name sortKey="Zhu, H" uniqKey="Zhu H">H Zhu</name>
</author>
<author>
<name sortKey="Mei, B" uniqKey="Mei B">B Mei</name>
</author>
<author>
<name sortKey="Wang, M" uniqKey="Wang M">M Wang</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Li, X" uniqKey="Li X">X Li</name>
</author>
<author>
<name sortKey="Redus, L" uniqKey="Redus L">L Redus</name>
</author>
<author>
<name sortKey="Chen, C" uniqKey="Chen C">C Chen</name>
</author>
<author>
<name sortKey="Martinez, Pa" uniqKey="Martinez P">PA Martinez</name>
</author>
<author>
<name sortKey="Strong, R" uniqKey="Strong R">R Strong</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Schmidt, S" uniqKey="Schmidt S">S Schmidt</name>
</author>
<author>
<name sortKey="Linnartz, B" uniqKey="Linnartz B">B Linnartz</name>
</author>
<author>
<name sortKey="Mendritzki, S" uniqKey="Mendritzki S">S Mendritzki</name>
</author>
<author>
<name sortKey="Sczepan, T" uniqKey="Sczepan T">T Sczepan</name>
</author>
<author>
<name sortKey="Lubbert, M" uniqKey="Lubbert M">M Lubbert</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Stichel, Cc" uniqKey="Stichel C">CC Stichel</name>
</author>
<author>
<name sortKey="Zhu, Xr" uniqKey="Zhu X">XR Zhu</name>
</author>
<author>
<name sortKey="Bader, V" uniqKey="Bader V">V Bader</name>
</author>
<author>
<name sortKey="Linnartz, B" uniqKey="Linnartz B">B Linnartz</name>
</author>
<author>
<name sortKey="Schmidt, S" uniqKey="Schmidt S">S Schmidt</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Scullin, Cs" uniqKey="Scullin C">CS Scullin</name>
</author>
<author>
<name sortKey="Tafoya, Lc" uniqKey="Tafoya L">LC Tafoya</name>
</author>
<author>
<name sortKey="Wilson, Mc" uniqKey="Wilson M">MC Wilson</name>
</author>
<author>
<name sortKey="Partridge, Ld" uniqKey="Partridge L">LD Partridge</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Martin, Sj" uniqKey="Martin S">SJ Martin</name>
</author>
<author>
<name sortKey="Grimwood, Pd" uniqKey="Grimwood P">PD Grimwood</name>
</author>
<author>
<name sortKey="Morris, Rg" uniqKey="Morris R">RG Morris</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Fallon, L" uniqKey="Fallon L">L Fallon</name>
</author>
<author>
<name sortKey="Moreau, F" uniqKey="Moreau F">F Moreau</name>
</author>
<author>
<name sortKey="Croft, Bg" uniqKey="Croft B">BG Croft</name>
</author>
<author>
<name sortKey="Labib, N" uniqKey="Labib N">N Labib</name>
</author>
<author>
<name sortKey="Gu, Wj" uniqKey="Gu W">WJ Gu</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Hanson, Je" uniqKey="Hanson J">JE Hanson</name>
</author>
<author>
<name sortKey="Orr, Al" uniqKey="Orr A">AL Orr</name>
</author>
<author>
<name sortKey="Madison, Dv" uniqKey="Madison D">DV Madison</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Saleewong, T" uniqKey="Saleewong T">T Saleewong</name>
</author>
<author>
<name sortKey="Srikiatkhachorn, A" uniqKey="Srikiatkhachorn A">A Srikiatkhachorn</name>
</author>
<author>
<name sortKey="Maneepark, M" uniqKey="Maneepark M">M Maneepark</name>
</author>
<author>
<name sortKey="Chonwerayuth, A" uniqKey="Chonwerayuth A">A Chonwerayuth</name>
</author>
<author>
<name sortKey="Bongsebandhu Phubhakdi, S" uniqKey="Bongsebandhu Phubhakdi S">S Bongsebandhu-phubhakdi</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Ranck, Jb" uniqKey="Ranck J">JB Ranck</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Otto, T" uniqKey="Otto T">T Otto</name>
</author>
<author>
<name sortKey="Eichenbaum, H" uniqKey="Eichenbaum H">H Eichenbaum</name>
</author>
<author>
<name sortKey="Wiener, Si" uniqKey="Wiener S">SI Wiener</name>
</author>
<author>
<name sortKey="Wible, Cg" uniqKey="Wible C">CG Wible</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Larson, J" uniqKey="Larson J">J Larson</name>
</author>
<author>
<name sortKey="Wong, D" uniqKey="Wong D">D Wong</name>
</author>
<author>
<name sortKey="Lynch, G" uniqKey="Lynch G">G Lynch</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">PLoS One</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosone</journal-id>
<journal-title-group>
<journal-title>PLoS ONE</journal-title>
</journal-title-group>
<issn pub-type="epub">1932-6203</issn>
<publisher>
<publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">25486126</article-id>
<article-id pub-id-type="pmc">4259468</article-id>
<article-id pub-id-type="publisher-id">PONE-D-14-39491</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0114216</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline-v2">
<subject>Biology and Life Sciences</subject>
<subj-group>
<subject>Biochemistry</subject>
</subj-group>
<subj-group>
<subject>Genetics</subject>
</subj-group>
<subj-group>
<subject>Molecular Biology</subject>
</subj-group>
<subj-group>
<subject>Neuroscience</subject>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v2">
<subject>Medicine and Health Sciences</subject>
<subj-group>
<subject>Neurology</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Behavioral Phenotyping of Parkin-Deficient Mice: Looking for Early Preclinical Features of Parkinson's Disease</article-title>
<alt-title alt-title-type="running-head">Behavioral Phenotyping of Parkin
<sup>−/−</sup>
Mice</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Rial</surname>
<given-names>Daniel</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Castro</surname>
<given-names>Adalberto A.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Machado</surname>
<given-names>Nuno</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Garção</surname>
<given-names>Pedro</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gonçalves</surname>
<given-names>Francisco Q.</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Silva</surname>
<given-names>Henrique B.</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tomé</surname>
<given-names>Ângelo R.</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Köfalvi</surname>
<given-names>Attila</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Corti</surname>
<given-names>Olga</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Raisman-Vozari</surname>
<given-names>Rita</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cunha</surname>
<given-names>Rodrigo A.</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff5">
<sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Prediger</surname>
<given-names>Rui D.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor1">
<sup>*</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1">
<label>1</label>
<addr-line>Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, 88049-900, SC, Brazil</addr-line>
</aff>
<aff id="aff2">
<label>2</label>
<addr-line>CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal</addr-line>
</aff>
<aff id="aff3">
<label>3</label>
<addr-line>CNRS UMR 7225, Hôpital de la Salpêtrière—Bâtiment, ICM (Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière), CRICM, Thérapeutique Expérimentale de la Neurodégénérescence, Université Pierre et Marie Curie, UPMC, 75651, Paris, France</addr-line>
</aff>
<aff id="aff4">
<label>4</label>
<addr-line>Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000-456, Coimbra, Portugal</addr-line>
</aff>
<aff id="aff5">
<label>5</label>
<addr-line>Faculty of Medicine, University of Coimbra, 3005-504, Coimbra, Portugal</addr-line>
</aff>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>Tort</surname>
<given-names>Adriano B. L.</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">
<addr-line>Federal University of Rio Grande do Norte, Brazil</addr-line>
</aff>
<author-notes>
<corresp id="cor1">* E-mail:
<email>ruidsp@hotmail.com</email>
</corresp>
<fn fn-type="conflict">
<p>
<bold>Competing Interests: </bold>
The authors have declared that no competing interests exist.</p>
</fn>
<fn fn-type="con">
<p>Conceived and designed the experiments: DR HBS ART AK OC RRV RAC RDP. Performed the experiments: DR AAC NM PG FQG HBS AK RDP. Analyzed the data: DR NM PG AK RDP. Contributed reagents/materials/analysis tools: AK OC RRV RAC RDP. Wrote the paper: DR AAC NM PG ART AK OC RRV RAC RDP.</p>
</fn>
</author-notes>
<pub-date pub-type="collection">
<year>2014</year>
</pub-date>
<pub-date pub-type="epub">
<day>8</day>
<month>12</month>
<year>2014</year>
</pub-date>
<volume>9</volume>
<issue>12</issue>
<elocation-id>e114216</elocation-id>
<history>
<date date-type="received">
<day>2</day>
<month>9</month>
<year>2014</year>
</date>
<date date-type="accepted">
<day>4</day>
<month>11</month>
<year>2014</year>
</date>
</history>
<permissions>
<copyright-year>2014</copyright-year>
<copyright-holder>Rial et al</copyright-holder>
<license>
<license-p>This is an open-access article distributed under the terms of the
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<abstract>
<p>There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson's disease (PD) begin many years before the appearance of the characteristic motor symptoms. Neuropsychiatric, sensorial and cognitive deficits are recognized as early non-motor manifestations of PD, and are not attenuated by the current anti-parkinsonian therapy. Although loss-of-function mutations in the
<italic>parkin</italic>
gene cause early-onset familial PD, Parkin-deficient mice do not display spontaneous degeneration of the nigrostriatal pathway or enhanced vulnerability to dopaminergic neurotoxins such as 6-OHDA and MPTP. Here, we employed adult homozygous C57BL/6 mice with
<italic>parkin</italic>
gene deletion on exon 3 (
<italic>parkin</italic>
<sup>−/−</sup>
) to further investigate the relevance of Parkin in the regulation of non-motor features, namely olfactory, emotional, cognitive and hippocampal synaptic plasticity.
<italic>Parkin</italic>
<sup>−/−</sup>
mice displayed normal performance on behavioral tests evaluating olfaction (olfactory discrimination), anxiety (elevated plus-maze), depressive-like behavior (forced swimming and tail suspension) and motor function (rotarod, grasping strength and pole). However,
<italic>parkin</italic>
<sup>−/−</sup>
mice displayed a poor performance in the open field habituation, object location and modified Y-maze tasks suggestive of procedural and short-term spatial memory deficits. These behavioral impairments were accompanied by impaired hippocampal long-term potentiation (LTP). These findings indicate that the genetic deletion of
<italic>parkin</italic>
causes deficiencies in hippocampal synaptic plasticity, resulting in memory deficits with no major olfactory, emotional or motor impairments. Therefore,
<italic>parkin</italic>
<sup>−/−</sup>
mice may represent a promising animal model to study the early stages of PD and for testing new therapeutic strategies to restore learning and memory and synaptic plasticity impairments in PD.</p>
</abstract>
<funding-group>
<funding-statement>This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-COFECUB 681-10), Programa de Apoio aos Núcleos de Excelência (PRONEX - Project NENASC), Fundação de Apoio à Pesquisa do Estado de Santa Catarina (FAPESC), QREN (CENTRO-07-ST24-FEDER-002006). DR and AAC received scholarships from CNPq. RDP is supported by a research fellowship from CNPq. RRV and RAC are supported by Visitant Research fellowships from CNPq (Ciência sem Fronteiras). The authors have no financial or personal conflicts of interest related to this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement>
</funding-group>
<counts>
<page-count count="21"></page-count>
</counts>
<custom-meta-group>
<custom-meta id="data-availability">
<meta-name>Data Availability</meta-name>
<meta-value>The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper.</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
<notes>
<title>Data Availability</title>
<p>The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper.</p>
</notes>
</front>
</pmc>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000094 | SxmlIndent | more

Ou

HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 000094 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Sante
   |area=    ParkinsonFranceV1
   |flux=    Pmc
   |étape=   Curation
   |type=    RBID
   |clé=     PMC:4259468
   |texte=   Behavioral Phenotyping of Parkin-Deficient Mice: Looking for Early Preclinical Features of Parkinson's Disease
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i   -Sk "pubmed:25486126" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd   \
       | NlmPubMed2Wicri -a ParkinsonFranceV1 

Wicri

This area was generated with Dilib version V0.6.29.
Data generation: Wed May 17 19:46:39 2017. Site generation: Mon Mar 4 15:48:15 2024