Abbott Louise C, Nahm Sang-Soep
Department of Veterinary Anatomy and Public Health, Texas A&M University, College Station, Texas 77843-4458, USA.
Cerebellum. 2004;3(3):141-51. doi: 10.1080/14734220410031927.
Nitric oxide (NO) is a diffusible, multifunctional signaling molecule found in many areas of the brain. NO signaling is involved in a wide array of neurophysiological functions including synaptogenesis, modulation of neurotransmitter release, synaptic plasticity, central nervous system blood flow and cell death. NO synthase (NOS) activity regulates the production of NO and the cerebellum expresses high levels of nitric oxide synthase (NOS) in granule, stellate and basket cells. Cerebellar mutant mice provide excellent opportunities to study changes of NO/NOS concentrations and activities to gain a greater understanding of the roles of NO and NOS in cerebellar function. Here, we have reviewed the current understanding of the functional roles of NO and NOS in the cerebellum and present NO/NOS activities that have been described in various cerebellar mutant mice and NOS knockout mice. NO appears to exert neuroprotective effects at low to moderate concentrations, whereas NO becomes neurotoxic as the concentration increases. Excessive NO production can cause oxidative stress to neurons, ultimately impairing neuronal function and result in neuronal cell death. Based on their genetics and cerebellar histopathology, some of cerebellar mutant mice display similarities with human neurological conditions and may prove to be valuable models to study several human neurological disorders, such as autism and schizophrenia.
一氧化氮（NO）是一种可扩散的多功能信号分子，存在于大脑的许多区域。NO信号传导参与多种神经生理功能，包括突触形成、神经递质释放的调节、突触可塑性、中枢神经系统血流和细胞死亡。一氧化氮合酶（NOS）的活性调节NO的产生，并且小脑在颗粒细胞、星状细胞和篮状细胞中表达高水平的一氧化氮合酶（NOS）。小脑突变小鼠为研究NO/NOS浓度和活性的变化提供了绝佳机会，以便更深入地了解NO和NOS在小脑功能中的作用。在此，我们综述了目前对NO和NOS在小脑中功能作用的理解，并介绍了在各种小脑突变小鼠和NOS基因敲除小鼠中所描述的NO/NOS活性。NO在低至中等浓度时似乎发挥神经保护作用，而随着浓度增加，NO会变得具有神经毒性。过量产生的NO可导致神经元氧化应激，最终损害神经元功能并导致神经元细胞死亡。基于它们的遗传学和小脑组织病理学，一些小脑突变小鼠与人类神经疾病表现出相似性，可能被证明是研究多种人类神经疾病（如自闭症和精神分裂症）的有价值模型。
