{"PubmedArticle":{"MedlineCitation":{"@attributes":{"Status":"MEDLINE","Owner":"NLM","IndexingMethod":"Automated"},"PMID":{"@attributes":{"Version":"1"},"@text":"36293496"},"DateCompleted":{"Year":"2022","Month":"10","Day":"28"},"DateRevised":{"Year":"2022","Month":"10","Day":"30"},"Article":{"@attributes":{"PubModel":"Electronic"},"Journal":{"ISSN":{"@attributes":{"IssnType":"Electronic"},"@text":"1422-0067"},"JournalIssue":{"@attributes":{"CitedMedium":"Internet"},"Volume":"23","Issue":"20","PubDate":{"Year":"2022","Month":"Oct","Day":"20"}},"Title":"International journal of molecular sciences","ISOAbbreviation":"Int J Mol Sci"},"ArticleTitle":"Abnormal Expression of Synaptic and Extrasynaptic GABA<sub>A<\/sub> Receptor Subunits in the Dystrophin-Deficient <i>mdx<\/i> Mouse.","ELocationID":[{"@attributes":{"EIdType":"pii","ValidYN":"Y"},"@text":"12617"},{"@attributes":{"EIdType":"doi","ValidYN":"Y"},"@text":"10.3390\/ijms232012617"}],"Abstract":{"AbstractText":["Duchenne muscular dystrophy (DMD) is a neurodevelopmental disorder primarily caused by the loss of the full-length Dp427 dystrophin in both muscle and brain. The basis of the central comorbidities in DMD is unclear. Brain dystrophin plays a role in the clustering of central gamma-aminobutyric acid A receptors (GABA<sub>A<\/sub>Rs), and its loss in the <i>mdx<\/i> mouse alters the clustering of some synaptic subunits in central inhibitory synapses. However, the diversity of GABAergic alterations in this model is still fragmentary. In this study, the analysis of in vivo PET imaging of a benzodiazepine-binding site radioligand revealed that the global density of central GABA<sub>A<\/sub>Rs is unaffected in <i>mdx<\/i> compared with WT mice. In contrast, semi-quantitative immunoblots and immunofluorescence confocal imaging in tissue sections revealed complex and differential patterns of alterations of the expression levels and\/or clustered distribution of a variety of synaptic and extrasynaptic GABA<sub>A<\/sub>R subunits in the hippocampus, cerebellum, cortex, and spinal cord. Hence, dystrophin loss not only affects the stabilization of synaptic GABA<sub>A<\/sub>Rs but also influences the subunit composition of GABA<sub>A<\/sub>Rs subtypes at both synaptic and extrasynaptic sites. This study provides new molecular outcome measures and new routes to evaluate the impact of treatments aimed at compensating alterations of the nervous system in DMD."]},"AuthorList":{"@attributes":{"CompleteYN":"Y"},"Author":[{"@attributes":{"ValidYN":"Y"},"LastName":"Zarrouki","ForeName":"Faouzi","Initials":"F","AffiliationInfo":[{"Affiliation":"Universit\u00e9 Paris-Saclay, CNRS, Institut des Neurosciences Paris Saclay, 91400 Saclay, France."},{"Affiliation":"Universit\u00e9 Paris-Saclay, UVSQ, Inserm, END-ICAP, 78000 Versailles, France."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Goutal","ForeName":"S\u00e9bastien","Initials":"S","AffiliationInfo":[{"Affiliation":"Universit\u00e9 Paris-Saclay, INSERM, CNRS, CEA, Laboratoire d'Imagerie Biom\u00e9dicale Multimodale (BioMaps), Service Hospitalier Fr\u00e9d\u00e9ric Joliot, 91401 Orsay, France."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Vacca","ForeName":"Oph\u00e9lie","Initials":"O","Identifier":[{"@attributes":{"Source":"ORCID"},"@text":"0000-0001-9281-843X"}],"AffiliationInfo":[{"Affiliation":"Universit\u00e9 Paris-Saclay, UVSQ, Inserm, END-ICAP, 78000 Versailles, France."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Garcia","ForeName":"Luis","Initials":"L","AffiliationInfo":[{"Affiliation":"Universit\u00e9 Paris-Saclay, UVSQ, Inserm, END-ICAP, 78000 Versailles, France."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Tournier","ForeName":"Nicolas","Initials":"N","Identifier":[{"@attributes":{"Source":"ORCID"},"@text":"0000-0002-0755-2030"}],"AffiliationInfo":[{"Affiliation":"Universit\u00e9 Paris-Saclay, INSERM, CNRS, CEA, Laboratoire d'Imagerie Biom\u00e9dicale Multimodale (BioMaps), Service Hospitalier Fr\u00e9d\u00e9ric Joliot, 91401 Orsay, France."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Goyenvalle","ForeName":"Aur\u00e9lie","Initials":"A","Identifier":[{"@attributes":{"Source":"ORCID"},"@text":"0000-0003-3938-1165"}],"AffiliationInfo":[{"Affiliation":"Universit\u00e9 Paris-Saclay, UVSQ, Inserm, END-ICAP, 78000 Versailles, France."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Vaillend","ForeName":"Cyrille","Initials":"C","Identifier":[{"@attributes":{"Source":"ORCID"},"@text":"0000-0002-8783-8185"}],"AffiliationInfo":[{"Affiliation":"Universit\u00e9 Paris-Saclay, CNRS, Institut des Neurosciences Paris Saclay, 91400 Saclay, France."}]}]},"Language":["eng"],"GrantList":{"@attributes":{"CompleteYN":"Y"},"Grant":[{"GrantID":"N\/A","Agency":"French National Centre for Scientific Research","Country":""},{"GrantID":"N\/A","Agency":"Inserm","Country":""},{"GrantID":"N\/A","Agency":"University of Paris-Saclay","Country":""},{"GrantID":"N\/A","Agency":"Conseil R\u00e9gional d'\u00cele-de-France","Country":""},{"GrantID":"N\/A","Agency":"Association Mon\u00e9gasque contre les Myopathies (AMM, Monaco)","Country":""},{"GrantID":"PhD fellowship","Agency":"French Muscular Dystrophy Association","Country":""},{"GrantID":"PhD fellowship","Agency":"Ministry of Higher Education and Research","Country":""},{"GrantID":"847826","Agency":"European Union's Horizon 2020 research and innovation","Country":""}]},"PublicationTypeList":{"PublicationType":[{"@attributes":{"UI":"D016428"},"@text":"Journal Article"}]},"ArticleDate":[{"@attributes":{"DateType":"Electronic"},"Year":"2022","Month":"10","Day":"20"}]},"MedlineJournalInfo":{"Country":"Switzerland","MedlineTA":"Int J Mol Sci","NlmUniqueID":"101092791","ISSNLinking":"1422-0067"},"ChemicalList":{"Chemical":[{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D016189"},"@text":"Dystrophin"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D011963"},"@text":"Receptors, GABA-A"}},{"RegistryNumber":"56-12-2","NameOfSubstance":{"@attributes":{"UI":"D005680"},"@text":"gamma-Aminobutyric Acid"}},{"RegistryNumber":"12794-10-4","NameOfSubstance":{"@attributes":{"UI":"D001569"},"@text":"Benzodiazepines"}}]},"CitationSubset":["IM"],"MeshHeadingList":{"MeshHeading":[{"DescriptorName":{"@attributes":{"UI":"D051379","MajorTopicYN":"N"},"@text":"Mice"}},{"DescriptorName":{"@attributes":{"UI":"D000818","MajorTopicYN":"N"},"@text":"Animals"}},{"DescriptorName":{"@attributes":{"UI":"D018101","MajorTopicYN":"N"},"@text":"Mice, Inbred mdx"}},{"DescriptorName":{"@attributes":{"UI":"D016189","MajorTopicYN":"Y"},"@text":"Dystrophin"},"QualifierName":[{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D011963","MajorTopicYN":"N"},"@text":"Receptors, GABA-A"},"QualifierName":[{"@attributes":{"UI":"Q000235","MajorTopicYN":"N"},"@text":"genetics"},{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D008810","MajorTopicYN":"N"},"@text":"Mice, Inbred C57BL"}},{"DescriptorName":{"@attributes":{"UI":"D020388","MajorTopicYN":"Y"},"@text":"Muscular Dystrophy, Duchenne"},"QualifierName":[{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D005680","MajorTopicYN":"N"},"@text":"gamma-Aminobutyric Acid"},"QualifierName":[{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D001569","MajorTopicYN":"N"},"@text":"Benzodiazepines"}}]},"KeywordList":[{"@attributes":{"Owner":"NOTNLM"},"Keyword":[{"@attributes":{"MajorTopicYN":"N"},"@text":"Duchenne muscular dystrophy"},{"@attributes":{"MajorTopicYN":"N"},"@text":"GABAA-receptor clustering"},{"@attributes":{"MajorTopicYN":"N"},"@text":"GABAergic synapses"},{"@attributes":{"MajorTopicYN":"N"},"@text":"PET brain imaging"},{"@attributes":{"MajorTopicYN":"N"},"@text":"immunofluorescence"},{"@attributes":{"MajorTopicYN":"N"},"@text":"outcome measures"},{"@attributes":{"MajorTopicYN":"N"},"@text":"western blots"}]}],"CoiStatement":"The authors declare no conflict of interest."},"PubmedData":{"History":{"PubMedPubDate":[{"@attributes":{"PubStatus":"received"},"Year":"2022","Month":"7","Day":"18"},{"@attributes":{"PubStatus":"revised"},"Year":"2022","Month":"9","Day":"21"},{"@attributes":{"PubStatus":"accepted"},"Year":"2022","Month":"10","Day":"11"},{"@attributes":{"PubStatus":"entrez"},"Year":"2022","Month":"10","Day":"27","Hour":"1","Minute":"24"},{"@attributes":{"PubStatus":"pubmed"},"Year":"2022","Month":"10","Day":"28","Hour":"6","Minute":"0"},{"@attributes":{"PubStatus":"medline"},"Year":"2022","Month":"10","Day":"29","Hour":"6","Minute":"0"},{"@attributes":{"PubStatus":"pmc-release"},"Year":"2022","Month":"10","Day":"20"}]},"PublicationStatus":"epublish","ArticleIdList":{"ArticleId":[{"@attributes":{"IdType":"pubmed"},"@text":"36293496"},{"@attributes":{"IdType":"pmc"},"@text":"PMC9604073"},{"@attributes":{"IdType":"doi"},"@text":"10.3390\/ijms232012617"},{"@attributes":{"IdType":"pii"},"@text":"ijms232012617"}]},"ReferenceList":[{"Reference":[{"Citation":"Desguerre 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