Hyperactive somatostatin interneurons contribute to excitotoxicity in neurodegenerative disorders

被引：122

作者：

Zhang, Wen ^{[1
]}

Zhang, Lifeng ^{[1
]}

Liang, Bo ^{[1
]}

Schroeder, David ^{[2
]}

Zhang, Zhong-wei ^{[2
]}

Cox, Gregory A. ^{[2
]}

Li, Yun ^{[1
]}

Lin, Da-Ting ^{[1
,2
]}

机构：

[1] NIDA, Intramural Res Program, NIH, Baltimore, MD USA

[2] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA

来源：

NATURE NEUROSCIENCE | 2016年 / 19卷 / 04期

关键词：

AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR CORTEX INHIBITION; TDP-43; ALS; MUTATIONS; NEURONS; RNA;

D O I：

10.1038/nn.4257

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping neurodegenerative disorders whose pathogenesis remains largely unknown. Using TDP-43(A315T) mice, an ALS and FTD model with marked cortical pathology, we found that hyperactive somatostatin interneurons disinhibited layer 5 pyramidal neurons (L5-PNs) and contributed to their excitotoxicity. Focal ablation of somatostatin interneurons efficiently restored normal excitability of L5-PNs and alleviated neurodegeneration, suggesting a new therapeutic target for ALS and FTD.

引用

页码：557 / +

页数：5

共 31 条

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