Breathing variability and brainstem serotonergic loss in a genetic model of multiple system atrophy.
Identifieur interne : 000045 ( France/Analysis ); précédent : 000044; suivant : 000046Breathing variability and brainstem serotonergic loss in a genetic model of multiple system atrophy.
Auteurs : Olivier Flabeau [France] ; Wassilios G. Meissner ; Annaig Ozier ; Patrick Berger ; François Tison ; Pierre-Olivier FernagutSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2014.
English descriptors
- KwdEn :
- MESH :
- genetics : Multiple System Atrophy.
- pathology : Brain Stem, Inclusion Bodies, Multiple System Atrophy, Neurons.
- physiopathology : Multiple System Atrophy.
- Animals, Disease Models, Animal, Humans, Male, Mice, Inbred C57BL, Models, Genetic, Respiration.
Abstract
Breathing disorders like sleep apnea, stridor, and dysrythmic breathing are frequent in patients with multiple system atrophy (MSA). These observations have been related to neurodegeneration in several pontomedullary respiratory nuclei and may explain the occurrence of sudden death. In this study, we sought to determine whether these functional and neuropathological characteristics could be replicated in a transgenic model of MSA. Mice expressing human wild-type α-synuclein under the control of the proteolipid promoter (PLP-αSYN) were compared with age-matched controls. Using whole-body, unrestrained plethysmography, the following breathing parameters were measured: inspiratory and expiratory times, tidal volume, expiratory volume, peak inspiratory and expiratory flows, and respiratory frequency. For each category, the mean, coefficient of variation, and irregularity score were analyzed. Brains were then processed for stereological cell counts of pontomedullary respiratory nuclei. A significant increase in the coefficient of variation and irregularity score was observed for inspiratory time, tidal volume, and expiratory volume in PLP-αSYN mice (P < 0.05). Glial cytoplasmic inclusions were found in the medullary raphe of PLP-αSYN mice, together with a loss of serotonergic immunoreactivity in the raphe obscurus (P < 0.001) and pallidus (P < 0.01). There was a negative correlation between α-synuclein burden and raphe pallidus cell counts (P < 0.05). There was no significant neuronal loss in the pre-Botzinger complex. The PLP-αSYN mouse model replicates the breathing variability and part of the neuronal depletion in pontomedullary respiratory nuclei observed in patients with MSA. Our findings support the use of this model for future candidate drugs in the breathing disorders observed in MSA.
DOI: 10.1002/mds.25804
PubMed: 24442757
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000605
- to stream PubMed, to step Curation: 000605
- to stream PubMed, to step Checkpoint: 000668
- to stream Ncbi, to step Merge: 003E92
- to stream Ncbi, to step Curation: 003E92
- to stream Ncbi, to step Checkpoint: 003E92
- to stream Main, to step Merge: 000651
- to stream Main, to step Curation: 000651
- to stream Main, to step Exploration: 000651
- to stream France, to step Extraction: 000045
Links to Exploration step
pubmed:24442757Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Breathing variability and brainstem serotonergic loss in a genetic model of multiple system atrophy.</title><author><name sortKey="Flabeau, Olivier" sort="Flabeau, Olivier" uniqKey="Flabeau O" first="Olivier" last="Flabeau">Olivier Flabeau</name><affiliation wicri:level="1"><nlm:affiliation>Service de Neurologie, Centre Hospitalier Universitaire de Bordeaux, Pessac, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Neurologie, Centre Hospitalier Universitaire de Bordeaux, Pessac</wicri:regionArea><wicri:noRegion>Pessac</wicri:noRegion><wicri:noRegion>Pessac</wicri:noRegion></affiliation></author><author><name sortKey="Meissner, Wassilios G" sort="Meissner, Wassilios G" uniqKey="Meissner W" first="Wassilios G" last="Meissner">Wassilios G. Meissner</name></author><author><name sortKey="Ozier, Annaig" sort="Ozier, Annaig" uniqKey="Ozier A" first="Annaig" last="Ozier">Annaig Ozier</name></author><author><name sortKey="Berger, Patrick" sort="Berger, Patrick" uniqKey="Berger P" first="Patrick" last="Berger">Patrick Berger</name></author><author><name sortKey="Tison, Francois" sort="Tison, Francois" uniqKey="Tison F" first="François" last="Tison">François Tison</name></author><author><name sortKey="Fernagut, Pierre Olivier" sort="Fernagut, Pierre Olivier" uniqKey="Fernagut P" first="Pierre-Olivier" last="Fernagut">Pierre-Olivier Fernagut</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24442757</idno><idno type="pmid">24442757</idno><idno type="doi">10.1002/mds.25804</idno><idno type="wicri:Area/PubMed/Corpus">000605</idno><idno type="wicri:Area/PubMed/Curation">000605</idno><idno type="wicri:Area/PubMed/Checkpoint">000668</idno><idno type="wicri:Area/Ncbi/Merge">003E92</idno><idno type="wicri:Area/Ncbi/Curation">003E92</idno><idno type="wicri:Area/Ncbi/Checkpoint">003E92</idno><idno type="wicri:Area/Main/Merge">000651</idno><idno type="wicri:Area/Main/Curation">000651</idno><idno type="wicri:Area/Main/Exploration">000651</idno><idno type="wicri:Area/France/Extraction">000045</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Breathing variability and brainstem serotonergic loss in a genetic model of multiple system atrophy.</title><author><name sortKey="Flabeau, Olivier" sort="Flabeau, Olivier" uniqKey="Flabeau O" first="Olivier" last="Flabeau">Olivier Flabeau</name><affiliation wicri:level="1"><nlm:affiliation>Service de Neurologie, Centre Hospitalier Universitaire de Bordeaux, Pessac, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Neurologie, Centre Hospitalier Universitaire de Bordeaux, Pessac</wicri:regionArea><wicri:noRegion>Pessac</wicri:noRegion><wicri:noRegion>Pessac</wicri:noRegion></affiliation></author><author><name sortKey="Meissner, Wassilios G" sort="Meissner, Wassilios G" uniqKey="Meissner W" first="Wassilios G" last="Meissner">Wassilios G. Meissner</name></author><author><name sortKey="Ozier, Annaig" sort="Ozier, Annaig" uniqKey="Ozier A" first="Annaig" last="Ozier">Annaig Ozier</name></author><author><name sortKey="Berger, Patrick" sort="Berger, Patrick" uniqKey="Berger P" first="Patrick" last="Berger">Patrick Berger</name></author><author><name sortKey="Tison, Francois" sort="Tison, Francois" uniqKey="Tison F" first="François" last="Tison">François Tison</name></author><author><name sortKey="Fernagut, Pierre Olivier" sort="Fernagut, Pierre Olivier" uniqKey="Fernagut P" first="Pierre-Olivier" last="Fernagut">Pierre-Olivier Fernagut</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Brain Stem (pathology)</term><term>Disease Models, Animal</term><term>Humans</term><term>Inclusion Bodies (pathology)</term><term>Male</term><term>Mice, Inbred C57BL</term><term>Models, Genetic</term><term>Multiple System Atrophy (genetics)</term><term>Multiple System Atrophy (pathology)</term><term>Multiple System Atrophy (physiopathology)</term><term>Neurons (pathology)</term><term>Respiration</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Multiple System Atrophy</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Brain Stem</term><term>Inclusion Bodies</term><term>Multiple System Atrophy</term><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Multiple System Atrophy</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Humans</term><term>Male</term><term>Mice, Inbred C57BL</term><term>Models, Genetic</term><term>Respiration</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Breathing disorders like sleep apnea, stridor, and dysrythmic breathing are frequent in patients with multiple system atrophy (MSA). These observations have been related to neurodegeneration in several pontomedullary respiratory nuclei and may explain the occurrence of sudden death. In this study, we sought to determine whether these functional and neuropathological characteristics could be replicated in a transgenic model of MSA. Mice expressing human wild-type α-synuclein under the control of the proteolipid promoter (PLP-αSYN) were compared with age-matched controls. Using whole-body, unrestrained plethysmography, the following breathing parameters were measured: inspiratory and expiratory times, tidal volume, expiratory volume, peak inspiratory and expiratory flows, and respiratory frequency. For each category, the mean, coefficient of variation, and irregularity score were analyzed. Brains were then processed for stereological cell counts of pontomedullary respiratory nuclei. A significant increase in the coefficient of variation and irregularity score was observed for inspiratory time, tidal volume, and expiratory volume in PLP-αSYN mice (P < 0.05). Glial cytoplasmic inclusions were found in the medullary raphe of PLP-αSYN mice, together with a loss of serotonergic immunoreactivity in the raphe obscurus (P < 0.001) and pallidus (P < 0.01). There was a negative correlation between α-synuclein burden and raphe pallidus cell counts (P < 0.05). There was no significant neuronal loss in the pre-Botzinger complex. The PLP-αSYN mouse model replicates the breathing variability and part of the neuronal depletion in pontomedullary respiratory nuclei observed in patients with MSA. Our findings support the use of this model for future candidate drugs in the breathing disorders observed in MSA.</div></front></TEI><affiliations><list><country><li>France</li></country></list><tree><noCountry><name sortKey="Berger, Patrick" sort="Berger, Patrick" uniqKey="Berger P" first="Patrick" last="Berger">Patrick Berger</name><name sortKey="Fernagut, Pierre Olivier" sort="Fernagut, Pierre Olivier" uniqKey="Fernagut P" first="Pierre-Olivier" last="Fernagut">Pierre-Olivier Fernagut</name><name sortKey="Meissner, Wassilios G" sort="Meissner, Wassilios G" uniqKey="Meissner W" first="Wassilios G" last="Meissner">Wassilios G. Meissner</name><name sortKey="Ozier, Annaig" sort="Ozier, Annaig" uniqKey="Ozier A" first="Annaig" last="Ozier">Annaig Ozier</name><name sortKey="Tison, Francois" sort="Tison, Francois" uniqKey="Tison F" first="François" last="Tison">François Tison</name></noCountry><country name="France"><noRegion><name sortKey="Flabeau, Olivier" sort="Flabeau, Olivier" uniqKey="Flabeau O" first="Olivier" last="Flabeau">Olivier Flabeau</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Santé/explor/MovDisordV3/Data/France/Analysis
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000045 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/France/Analysis/biblio.hfd -nk 000045 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Santé
|area= MovDisordV3
|flux= France
|étape= Analysis
|type= RBID
|clé= pubmed:24442757
|texte= Breathing variability and brainstem serotonergic loss in a genetic model of multiple system atrophy.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/France/Analysis/RBID.i -Sk "pubmed:24442757" \
| HfdSelect -Kh $EXPLOR_AREA/Data/France/Analysis/biblio.hfd \
| NlmPubMed2Wicri -a MovDisordV3
| This area was generated with Dilib version V0.6.23. |  |