title: Short communication: altered synaptic clustering of GABAA receptors in mice lacking dystrophin (mdx mice).
abstract: Dystrophin is selectively localized in the postsynaptic density of neurons in cerebral cortex, hippocampus and cerebellum. Here, we show by double-immunofluorescence staining that dystrophin is extensively colocalized with GABAA receptor subunit clusters in these brain regions. To determine the relevance of this observation, we investigated in mdx mice, which provide a model of Duchenne muscular dystrophy, whether the absence of dystrophin affects the synaptic clustering of GABAA receptors. A marked reduction in the number of clusters immunoreactive for the alpha1 and alpha2 subunits was observed in, respectively, cerebellum and hippocampus of mdx mice, but not in striatum, which is normally devoid of dystrophin. Furthermore, these alterations were not accompanied by a change in gephyrin staining, although gephyrin is colocalized with the majority of GABAA receptor clusters in these regions. These results indicate that dystrophin may play an important role in the clustering or stabilization of GABAA receptors in a subset of central inhibitory synapses. These deficits may underlie the cognitive impairment seen in Duchenne patients.
authors.affiliation: Institute of Pharmacology, University of Zurich, Switzerland.
authors.forename: I
authors.initials: I
authors.lastname: Knuesel
authors.forename: M
authors.initials: M
authors.lastname: Mastrocola
authors.forename: R A
authors.initials: RA
authors.lastname: Zuellig
authors.forename: B
authors.initials: B
authors.lastname: Bornhauser
authors.forename: M C
authors.initials: MC
authors.lastname: Schaub
authors.forename: J M
authors.initials: JM
authors.lastname: Fritschy
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D016189:Dystrophin / Q000172:deficiency* / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D046911:Macromolecular Substances; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009137:Muscular Dystrophy, Animal / Q000378:metabolism*; D019579:Neocortex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D002352:Carrier Proteins; D016189:Dystrophin; D046911:Macromolecular Substances; D008565:Membrane Proteins; D011963:Receptors, GABA-A; C073441:gephyrin