Neuroimmune regulation of neurophysiology in the cerebellum.
Neuroimmune regulation of neurophysiology in the cerebellum.
复制标题
DOI：
10.1007/s12311-012-0445-8
复制
发表时间：
2013-06
期刊：
影响因子：
3.5
通讯作者：
Gruol, Donna L.
中科院分区：
文献类型：
--
作者：
Gruol, Donna L.
最近的研究已经确定了先天免疫系统在中枢神经系统（CNS）中的存在，并暗示了该系统在正常和病理过程中的关键作用。星形胶质细胞和小胶质细胞是中枢神经系统的正常组成部分，是构成中枢神经系统先天免疫系统的主要细胞类型。它们在正常和不良条件下的基本作用是产生神经免疫因子，如细胞因子和趋化因子，它们是启动或协调下游细胞活动的信号分子。在不利条件下，细胞因子和趋化因子在防御和修复中起作用。然而，如果这些因子的表达失调，就会导致中枢神经系统功能异常。中枢神经系统的神经元和神经胶质细胞都表达细胞因子和趋化因子的受体，但受体激活的生物学后果尚未完全解决。我们的研究表明，在细胞因子白介素-6 （IL-6）长期处理的大鼠小脑细胞和在CNS中长期表达高水平IL-6的转基因小鼠的小脑中，神经适应性变化产生。在培养和活体小脑中，神经适应性变化包括参与基因表达、信号转导和突触传递的蛋白质表达水平的改变。与这些变化相关的是神经元功能的改变。对培养的小脑细胞和转基因小鼠小脑的比较结果表明，IL-6的作用在不同的神经元类型中是不同的。然而，在所有的细胞类型中都观察到Ca2+稳态机制的改变。这些结果表明，小脑功能的改变可能发生在与小脑IL-6水平升高相关的疾病中。
Recent studies have established the existence of an innate immune system in the central nervous system (CNS) and implicated a critical role for this system in both normal and pathological processes. Astrocytes and microglia, normal components of the CNS, are the primary cell types that comprise the innate immune system of the CNS. Basic to their role during normal and adverse conditions is the production of neuroimmune factors such as cytokines and chemokines, which are signaling molecules that initiate or coordinate downstream cellular actions. During adverse conditions, cytokines and chemokines function in defensive and repair. However, if expression of these factors becomes dysregulated, abnormal CNS function can result. Both neurons and glial cells of the CNS express receptors for cytokines and chemokines, but the biological consequence of receptor activation has yet to be fully resolved. Our studies show that neuroadaptive changes are produced in primary cultures of rat cerebellar cells chronically treated with the cytokine interleukin-6 (IL-6) and in the cerebellum of transgenic mice that chronically express elevated levels of IL-6 in the CNS. In the cerebellum in culture and in vivo, the neuroadaptive changes included alterations in the level of expression of proteins involved in gene expression, signal transduction, and synaptic transmission. Associated with these changes were alterations in neuronal function. A comparison of results from the cultured cerebellar cells and cerebellum of the transgenic mice indicated that the effects of IL-6 can vary across neuronal types. However, alterations in mechanisms involved in Ca2+ homeostasis were observed in all cell types studied. These results indicate that modifications in cerebellar function are likely to occur in disorders associated with elevated levels of IL-6 in the cerebellum.
登录
查看更多内容
影响因子：
2.9
作者：
Luzi, Paola;Abraham, Ronnie M.;Rafi, Mohammad A.;Curtis, Mark;Hooper, D. Craig;Wenger, David A.
通讯作者：
Wenger, David A.
影响因子：
3.6
作者：
Bae, Jae-sung;Carter, Janet E.;Jin, Hee Kyung
通讯作者：
Jin, Hee Kyung
影响因子：
9.3
作者：
Wei H;Zou H;Sheikh AM;Malik M;Dobkin C;Brown WT;Li X
通讯作者：
Li X
DOI：
10.1073/pnas.92.7.3032
发表时间：
1995-03-28
影响因子：
11.1
作者：
BRUGG, B;DUBREUIL, YL;MARIANI, J
通讯作者：
MARIANI, J
影响因子：
4.2
作者：
Tomita, M;Holman, BJ;Santoro, TJ
通讯作者：
Santoro, TJ