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  • 标题:Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes
  • 本地全文:下载
  • 作者:Michael E. Cahill ; Zhong Xie ; Michelle Day
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2009
  • 卷号:106
  • 期号:31
  • 页码:13058-13063
  • DOI:10.1073/pnas.0904636106
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Dendritic spine morphogenesis contributes to brain function, cognition, and behavior, and is altered in psychiatric disorders. Kalirin is a brain-specific guanine-nucleotide exchange factor (GEF) for Rac-like GTPases and is a key regulator of spine morphogenesis. Here, we show that KALRN-knockout mice have specific reductions in cortical, but not hippocampal, Rac1 signaling and spine density, and exhibit reduced cortical glutamatergic transmission. These mice exhibit robust deficits in working memory, sociability, and prepulse inhibition, paralleled by locomotor hyperactivity reversible by clozapine in a kalirin-dependent manner. Several of these deficits are delayed and age-dependent. Our study thus links spine morphogenic signaling with age-dependent, delayed, disease-related phenotypes, including cognitive dysfunction.
  • 关键词:prefrontal cortex ; kalirin-7 ; schizophrenia ; Alzheimer's disease ; synaptic plasticity
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