Abnormal striatal GABA transmission in the mouse model for the fragile X syndrome.

Détails

ID Serval
serval:BIB_82100D8A043E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Abnormal striatal GABA transmission in the mouse model for the fragile X syndrome.
Périodique
Biological psychiatry
Auteur(s)
Centonze D., Rossi S., Mercaldo V., Napoli I., Ciotti M.T., De Chiara V., Musella A., Prosperetti C., Calabresi P., Bernardi G., Bagni C.
ISSN
1873-2402 (Electronic)
ISSN-L
0006-3223
Statut éditorial
Publié
Date de publication
15/05/2008
Volume
63
Numéro
10
Pages
963-973
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Structural and functional neuroimaging studies suggest abnormal activity in the striatum of patients with the fragile X syndrome (FXS), the most common form of inherited mental retardation.
Neurophysiological and immunofluorescence experiments in striatal brain slices. We studied the synaptic transmission in a mouse model for FXS, as well as the subcellular localization of fragile X mental retardation protein (FMRP) and brain cytoplasmic (BC1) RNA in striatal axons.
Our results show that absence of FMRP is associated with apparently normal striatal glutamate-mediated transmission, but abnormal gamma-aminobutyric acid (GABA) transmission. This effect is likely secondary to increased transmitter release from GABAergic nerve terminals. We detected the presence of FMRP in axons of striatal neurons and observed a selective increase in the frequency of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs, mIPSCs) in fmr1-knockout mice. We also observed reduced paired-pulse ratio of evoked IPSCs, a finding that is consistent with the idea that transmitter release probability from striatal GABAergic nerve terminals is higher than normal in these mutants. Finally, we have identified the small noncoding BC1 RNA as a critical coplayer of FMRP in the regulation of striatal synaptic transmission.
Understanding the physiologic action of FMRP and the synaptic defects associated with GABA transmission might be useful to design appropriate pharmacologic interventions for FXS.

Mots-clé
Animals, Cerebral Cortex/pathology, Cerebral Cortex/physiopathology, Corpus Striatum/metabolism, Corpus Striatum/pathology, Disease Models, Animal, Electric Stimulation/methods, Fragile X Mental Retardation Protein/genetics, Fragile X Mental Retardation Protein/metabolism, Fragile X Syndrome/genetics, Fragile X Syndrome/pathology, Fragile X Syndrome/physiopathology, Gene Expression Regulation/genetics, In Vitro Techniques, Mice, Mice, Inbred C57BL, Mice, Knockout, Neural Inhibition/genetics, Neural Inhibition/radiation effects, Patch-Clamp Techniques/methods, Phalloidine/metabolism, RNA, Long Noncoding, RNA, Untranslated, Ribonucleoproteins, Small Cytoplasmic/deficiency, Synaptic Transmission/genetics, Synaptic Transmission/physiology, Vesicular Inhibitory Amino Acid Transport Proteins/metabolism, gamma-Aminobutyric Acid/metabolism
Pubmed
Création de la notice
06/03/2017 18:23
Dernière modification de la notice
03/03/2018 18:49
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