Nocturnal motor coordination deficits in neuronal nitric oxide synthase knock-out mice
Nocturnal motor coordination deficits in neuronal nitric oxide synthase knock-out mice
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DOI：
10.1016/s0306-4522(98)00614-9
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发表时间：
1999-03-01
期刊：
影响因子：
3.3
通讯作者：
Snyder, SH
中科院分区：
文献类型：
--
作者：
Kriegsfeld, LJ;Eliasson, MJL;Snyder, SH
一氧化氮主要由含有神经元型一氧化氮合酶（nNOS）的神经元在脑中形成，尽管一些神经元可能表达内皮型NOS（eNOS），并且诱导型NOS（iNOS）仅在毒性刺激后的神经元中出现（4、5、12）。具有nNOS靶向破坏（nNOS（-））的小鼠显示胃膨胀，幽门括约肌肥大，反映肌间神经丛神经元中nNOS的损失。(7)nNOS（-）动物抵抗大脑中动脉闭塞后的脑损伤（8），这与过量释放一氧化氮介导缺血性中风中的神经毒性的证据一致。（3）神经元NOS-小鼠在运动活动、繁殖（10）小脑中的长时程抑制、（9）海马中的长时程增强、（11）和总体感觉运动功能方面没有明显的缺陷。(10)然而，nNOS（-）动物表现出过度的，不适当的性行为和侵略性的急剧增加（10）因为小脑在大脑中拥有最高水平的nNOS神经元，令人惊讶的是，假定的小脑功能，如平衡和协调，在nNOS（-）小鼠中是非常正常的。这些以前的研究都是在白天进行的（1400和1600之间，0700开灯），我们现在报告nNOS（-）小鼠在夜间选择性反映的平衡和运动协调的显著，离散的异常。(C)1998年IBRO。出版社：Elsevier Science Ltd
Nitric oxide is formed in the brain primarily by neurons containing neuronal nitric oxide synthase (nNOS), though some neurons may express endothelial NOS (eNOS), and inducible NOS (iNOS) only occurs in neurons following toxic stimuli(4,5,12) Mice with targeted disruption of nNOS (nNOS(-)) display distended stomachs with hypertrophied pyloric sphincters reflecting loss of nNOS in myenteric plexus neurons.(7) nNOS(-) animals resist brain damage following middle cerebral artery occlusions(8) consistent with evidence that excess release of nitric oxide mediates neurotoxicity in ischemic stroke.(3)Neuronal NOS- mice have no grossly evident defects in locomotor activity, breeding(10) long-term depression in the cerebellum,(9) long-term potentiation in the hippocampus,(l1) and overall sensorimotor function.(10) However, nNOS(-) animals display excessive, inappropriate sexual behavior and dramatic increases in aggression (10) Because the cerebellum possesses the greatest levels of nNOS neurons in the brain, it was surprising that presumed cerebellar functions such as balance and coordination were grossly normal in nNOS(-) mice. These previous studies were all conducted during the day (between 1400 and 1600, lights on at 0700), We now report striking, discrete abnormalities in balance and motor coordination in nNOS(-) mice reflected selectively at night. (C) 1998 IBRO. Published by Elsevier Science Ltd.