DISRUPTION OF CIC-2 EXPRESSION IS ASSOCIATED WITH PROGRESSIVE NEURODEGENERATION IN AGING MICE
DISRUPTION OF CIC-2 EXPRESSION IS ASSOCIATED WITH PROGRESSIVE NEURODEGENERATION IN AGING MICE
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DOI：
10.1016/j.neuroscience.2010.01.042
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发表时间：
2010-04-28
期刊：
影响因子：
3.3
通讯作者：
Bear, C. E.
中科院分区：
文献类型：
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作者：
Cortez, M. A.;Li, C.;Bear, C. E.
CIC-2的杂合突变在罕见病例中与全身性、特发性癫痫的易感性增加相关。最初，假设CIC-2的突变可能与癫痫相关，因为CIC-2在海马神经元兴奋性的改变中起直接作用。然而，年轻的CIC-2敲除（KO）小鼠中缺乏明显的癫痫发作易感性表型，使得这一假设变得令人难以置信。最近对老年CIC-2 KO小鼠（> 6个月）的一项研究显示，中央轴突的髓鞘异常，以及中央听觉通路中神经元功能的微妙缺陷。这些发现促使我们重新检查老年CIC-2 KO小鼠海马神经元的形态和兴奋性。有趣的是，在老年小鼠中获得的皮质电图记录显示自发性发作间期尖峰，这是海马神经传递扰动的标志，从而增加兴奋。这种电生理缺陷与星形胶质细胞激活和这些老年小鼠海马CA3区神经元变性的证据有关。总之，这些发现提高了CIC-2表达在老化海马中发挥微妙的神经保护作用的可能性。(C)2010年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Heterozygous mutations in CIC-2 have been associated in rare cases with increased susceptibility to generalized, idiopathic epilepsy. Initially, it was hypothesized that mutations in CIC-2 may be associated with epilepsy due to a direct role for CIC-2 in the modification of hippocampal neuronal excitability. However, the absence of an overt seizure-susceptibility phenotype in young CIC-2 knockout (KO) mice rendered this hypothesis- implausible. A recent study of older CIC-2 KO mice (>6 months) revealed abnormalities in the myelin of central axons and a subtle defect in the neuronal function in the central auditory pathway. These findings prompted us to re-examine hippocampal neuron morphology and excitability in older CIC-2 KO mice. Interestingly, electrocorticographic recordings obtained in older mice revealed spontaneous interictal spikes which are a marker of perturbed hippocampal neurotransmission with a resultant increase in excitation. This electrophysiological defect was associated with astrocyte activation and evidence of neuronal degeneration in the CA3 region of the hippocampus of these older mice. Together, these findings raise the possibility that CIC-2 expression plays a subtle neuroprotective role in the aging hippocampus. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.