Altered synaptic clustering of GABA(A) receptors in mice lacking dystrophin (mdx mice)

Citation
I. Knuesel et al., Altered synaptic clustering of GABA(A) receptors in mice lacking dystrophin (mdx mice), EUR J NEURO, 11(12), 1999, pp. 4457-4462
Citations number
15
Categorie Soggetti
Neurosciences & Behavoir
Journal title
EUROPEAN JOURNAL OF NEUROSCIENCE
ISSN journal
0953816X → ACNP
Volume
11
Issue
12
Year of publication
1999
Pages
4457 - 4462
Database
ISI
SICI code
0953-816X(199912)11:12<4457:ASCOGR>2.0.ZU;2-W
Abstract
Dystrophin is selectively localized in the postsynaptic density of neurons in cerebral cortex, hippocampus and cerebellum. Here, we show by double-imm unofluorescence staining that dystrophin is extensively colocalized with GA BA(A) receptor subunit clusters in these brain regions. To determine the re levance of this observation, we investigated in mdx mice, which provide a m odel of Duchenne muscular dystrophy, whether the absence of dystrophin affe cts the synaptic clustering of GABA(A) receptors. A marked reduction in the number of clusters immunoreactive for the alpha 1 and alpha 2 subunits was observed in, respectively, cerebellum and hippocampus of mdx mice, but not in striatum, which is normally devoid of dystrophin. Furthermore, these al terations were not accompanied by a change in gephyrin staining, although g ephyrin is colocalized with the majority of GABA(A) receptor clusters in th ese regions. These results indicate that dystrophin may play an important r ole in the clustering or stabilization of GABA(A) receptors in a subset of central inhibitory synapses. These deficits may underlie the cognitive impa irment seen in Duchenne patients.