Behavioral Phenotyping of Parkin-Deficient Mice: Looking for Early Preclinical Features of Parkinson's Disease
Identifieur interne : 000A43 ( Main/Exploration ); précédent : 000A42; suivant : 000A44Behavioral 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 :
- PLoS ONE [ 1932-6203 ] ; 2014.
English descriptors
- KwdEn :
- Animals, Behavior, Animal, Disease Models, Animal, Dopamine (metabolism), Gene Deletion, Hippocampus (metabolism), Hippocampus (physiopathology), Homozygote, Locomotion, Long-Term Potentiation, Male, Memory, Mice, Mice, Knockout, Motor Activity, Nerve Endings (metabolism), Parkinson Disease (diagnosis), Parkinson Disease (genetics), Parkinson Disease (physiopathology), Phenotype, Ubiquitin-Protein Ligases (deficiency), Ubiquitin-Protein Ligases (genetics).
- MESH :
- chemical , deficiency : Ubiquitin-Protein Ligases.
- chemical , genetics : Ubiquitin-Protein Ligases.
- chemical , metabolism : Dopamine.
- diagnosis : Parkinson Disease.
- genetics : Parkinson Disease.
- metabolism : Hippocampus, Nerve Endings.
- physiopathology : Hippocampus, Parkinson Disease.
- Animals, Behavior, Animal, Disease Models, Animal, Gene Deletion, Homozygote, Locomotion, Long-Term Potentiation, Male, Memory, Mice, Mice, Knockout, Motor Activity, Phenotype.
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
Url:
DOI: 10.1371/journal.pone.0114216
PubMed: 25486126
PubMed Central: 4259468
Affiliations:
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Le document en format XML
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Castro</name><affiliation wicri:level="2"><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><placeName><region type="state">Santa Catarina</region></placeName></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><wicri:noRegion>Coimbra</wicri:noRegion></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><wicri:noRegion>Coimbra</wicri:noRegion></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><wicri:noRegion>Coimbra</wicri:noRegion></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><wicri:noRegion>Coimbra</wicri:noRegion></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><wicri:noRegion>Coimbra</wicri:noRegion></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><wicri:noRegion>Coimbra</wicri:noRegion></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><wicri:noRegion>Coimbra</wicri:noRegion></affiliation></author><author><name sortKey="Corti, Olga" sort="Corti, Olga" uniqKey="Corti O" first="Olga" last="Corti">Olga Corti</name><affiliation wicri:level="4"><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><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></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="4"><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><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></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><wicri:noRegion>Coimbra</wicri:noRegion></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><wicri:noRegion>Coimbra</wicri:noRegion></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="2"><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><placeName><region type="state">Santa Catarina</region></placeName></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><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Behavior, Animal</term><term>Disease Models, Animal</term><term>Dopamine (metabolism)</term><term>Gene Deletion</term><term>Hippocampus (metabolism)</term><term>Hippocampus (physiopathology)</term><term>Homozygote</term><term>Locomotion</term><term>Long-Term Potentiation</term><term>Male</term><term>Memory</term><term>Mice</term><term>Mice, Knockout</term><term>Motor Activity</term><term>Nerve Endings (metabolism)</term><term>Parkinson Disease (diagnosis)</term><term>Parkinson Disease (genetics)</term><term>Parkinson Disease (physiopathology)</term><term>Phenotype</term><term>Ubiquitin-Protein Ligases (deficiency)</term><term>Ubiquitin-Protein Ligases (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="deficiency" xml:lang="en"><term>Ubiquitin-Protein Ligases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Ubiquitin-Protein Ligases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Hippocampus</term><term>Nerve Endings</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Hippocampus</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Behavior, Animal</term><term>Disease Models, Animal</term><term>Gene Deletion</term><term>Homozygote</term><term>Locomotion</term><term>Long-Term Potentiation</term><term>Male</term><term>Memory</term><term>Mice</term><term>Mice, Knockout</term><term>Motor Activity</term><term>Phenotype</term></keywords></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 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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><affiliations><list><country><li>Brésil</li><li>France</li><li>Portugal</li></country><region><li>Santa Catarina</li><li>Île-de-France</li></region><settlement><li>Paris</li></settlement><orgName><li>Université Pierre-et-Marie-Curie</li></orgName></list><tree><country name="Brésil"><region name="Santa Catarina"><name sortKey="Rial, Daniel" sort="Rial, Daniel" uniqKey="Rial D" first="Daniel" last="Rial">Daniel Rial</name></region><name sortKey="Castro, Adalberto A" sort="Castro, Adalberto A" uniqKey="Castro A" first="Adalberto A." last="Castro">Adalberto A. Castro</name><name sortKey="Prediger, Rui D" sort="Prediger, Rui D" uniqKey="Prediger R" first="Rui D." last="Prediger">Rui D. Prediger</name></country><country name="Portugal"><noRegion><name sortKey="Rial, Daniel" sort="Rial, Daniel" uniqKey="Rial D" first="Daniel" last="Rial">Daniel Rial</name></noRegion><name sortKey="Cunha, Rodrigo A" sort="Cunha, Rodrigo A" uniqKey="Cunha R" first="Rodrigo A." last="Cunha">Rodrigo A. Cunha</name><name sortKey="Cunha, Rodrigo A" sort="Cunha, Rodrigo A" uniqKey="Cunha R" first="Rodrigo A." last="Cunha">Rodrigo A. Cunha</name><name sortKey="Garcao, Pedro" sort="Garcao, Pedro" uniqKey="Garcao P" first="Pedro" last="Garção">Pedro Garção</name><name sortKey="Goncalves, Francisco Q" sort="Goncalves, Francisco Q" uniqKey="Goncalves F" first="Francisco Q." last="Gonçalves">Francisco Q. Gonçalves</name><name sortKey="Kofalvi, Attila" sort="Kofalvi, Attila" uniqKey="Kofalvi A" first="Attila" last="Köfalvi">Attila Köfalvi</name><name sortKey="Machado, Nuno" sort="Machado, Nuno" uniqKey="Machado N" first="Nuno" last="Machado">Nuno Machado</name><name sortKey="Silva, Henrique B" sort="Silva, Henrique B" uniqKey="Silva H" first="Henrique B." last="Silva">Henrique B. Silva</name><name sortKey="Tome, Angelo R" sort="Tome, Angelo R" uniqKey="Tome A" first="Ângelo R." last="Tomé">Ângelo R. Tomé</name><name sortKey="Tome, Angelo R" sort="Tome, Angelo R" uniqKey="Tome A" first="Ângelo R." last="Tomé">Ângelo R. Tomé</name></country><country name="France"><region name="Île-de-France"><name sortKey="Corti, Olga" sort="Corti, Olga" uniqKey="Corti O" first="Olga" last="Corti">Olga Corti</name></region><name sortKey="Raisman Vozari, Rita" sort="Raisman Vozari, Rita" uniqKey="Raisman Vozari R" first="Rita" last="Raisman-Vozari">Rita Raisman-Vozari</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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