| RRC ID |
17568
|
| 著者 |
Beguin S, Crépel V, Aniksztejn L, Becq H, Pelosi B, Pallesi-Pocachard E, Bouamrane L, Pasqualetti M, Kitamura K, Cardoso C, Represa A.
|
| タイトル |
An epilepsy-related ARX polyalanine expansion modifies glutamatergic neurons excitability and morphology without affecting GABAergic neurons development.
|
| ジャーナル |
Cereb Cortex
|
| Abstract |
Epileptic encephalopathies comprise a heterogeneous group of severe infantile disorders for which the pathophysiological basis of epilepsy is inaccurately clarified by genotype-phenotype analysis. Because a deficit of GABA neurons has been found in some of these syndromes, notably in patients with X-linked lissencephaly with abnormal genitalia, epilepsy was suggested to result from an imbalance in GABAergic inhibition, and the notion of "interneuronopathy" was proposed. Here, we studied the impact of a polyalanine expansion of aristaless-related homeobox (ARX) gene, a mutation notably found in West and Ohtahara syndromes. Analysis of Arx((GCG)7/Y) knock-in mice revealed that GABA neuron development is not affected. Moreover, pyramidal cell migration and cortical layering are unaltered in these mice. Interestingly, electrophysiological recordings show that hippocampal pyramidal neurons displayed a frequency of inhibitory postsynaptic currents similar to wild-type (WT) mice. However, these neurons show a dramatic increase in the frequency of excitatory inputs associated with a remodeling of their axonal arborization, suggesting that epilepsy in Arx((GCG)7/Y)mice would result from a glutamate network remodeling. We therefore propose that secondary alterations are instrumental for the development of disease-specific phenotypes and should be considered to explain the phenotypic diversity associated with epileptogenic mutations.
|
| 巻・号 |
23(6)
|
| ページ |
1484-94
|
| 公開日 |
2013-6-1
|
| DOI |
10.1093/cercor/bhs138
|
| PII |
bhs138
|
| PMID |
22628459
|
| MeSH |
6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
Action Potentials / drug effects
Action Potentials / genetics
Age Factors
Animals
Animals, Newborn
Cell Movement / genetics
Doublecortin Protein
Electroporation
Embryo, Mammalian
Excitatory Amino Acid Antagonists / pharmacology
Female
GABAergic Neurons / cytology
GABAergic Neurons / physiology*
Gene Expression Regulation, Developmental / genetics*
Glutamate Decarboxylase / metabolism
Glutamates / metabolism*
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
HEK293 Cells
Homeodomain Proteins / genetics*
Humans
Lysine / analogs & derivatives
Lysine / metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Nerve Tissue Proteins / metabolism
Organ Culture Techniques
Patch-Clamp Techniques
Peptides / genetics*
RNA, Small Interfering / genetics
Statistics, Nonparametric
Synaptic Potentials / drug effects
Synaptic Potentials / genetics
Transcription Factors / genetics*
Transfection
gamma-Aminobutyric Acid / metabolism*
|
| IF |
5.043
|
| 引用数 |
26
|
|
WOS 分野
|
NEUROSCIENCES
|
| リソース情報 |
| 実験動物マウス |
RBRC03654 |
