論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC03654 |