Altered synaptic transmission in the hippocampus of transgenic mice with enhanced central nervous systems expression of interleukin-6.
Altered synaptic transmission in the hippocampus of transgenic mice with enhanced central nervous systems expression of interleukin-6.
复制标题
DOI：
10.1016/j.bbi.2012.05.005
复制
发表时间：
2012-08
影响因子：
15.1
通讯作者：
Gruol, D. L.
中科院分区：
文献类型：
--
作者：
Nelson, T. E.;Engberink, A. Olde;Hernandez, R.;Puro, A.;Huitron-Resendiz, S.;Hao, C.;De Graan, P. N. E.;Gruol, D. L.
关键词：
炎性细胞因子白细胞介素-6（IL-6）水平升高发生在许多CNS疾病中。然而，很少有人知道这种情况如何影响中枢神经系统的神经功能。在CNS中表达升高水平的IL-6的转基因小鼠显示认知变化、海马癫痫发作的倾向增加和抑制性中间神经元的数量减少，这表明升高水平的IL-6可引起改变海马功能的神经适应性变化。为了确定这些神经适应性变化，我们测量了蛋白质表达水平，使用Western印迹分析和突触功能，使用场电位记录在海马从IL-6转基因小鼠（IL-6 tg）和他们的非转基因（non-tg）同窝出生。Western blot分析显示，与非tg海马相比，IL-6 tg海马中GFAP和STAT 3的水平增强，但其他几种蛋白质没有差异。场电位记录的突触传递在Schaffer侧支CA 1突触表现出增强树突兴奋性突触后电位和体细胞群体尖峰在CA 1区的海马切片从IL-6 TG小鼠与切片从非TG同窝对照。从IL-6 tg和非tg小鼠海马切片之间的短期和长期突触可塑性的几种形式没有观察到差异。这些结果表明，IL-6水平升高可以改变海马神经元和突触的兴奋性所涉及的机制，这一效应与最近的证据一致，表明IL-6的产生升高在与癫痫发作活动相关的病症中以及在具有神经炎性成分的CNS疾病中观察到的其他损伤中起重要作用。
Elevated levels of the inflammatory cytokine interleukin-6 (IL-6) occur in a number of CNS disorders. However, little is known about how this condition affects CNS neuronal function. Transgenic mice that express elevated levels of IL-6 in the CNS show cognitive changes, increased propensity for hippocampal seizures and reduced number of inhibitory interneurons, suggesting that elevated levels of IL-6 can cause neuroadaptive changes that alter hippocampal function. To identify these neuroadaptive changes, we measured the levels of protein expression using Western blot analysis and synaptic function using field potential recordings in hippocampus from IL-6 transgenic mice (IL-6 tg) and their non-transgenic (non-tg) littermates. Western blot analysis showed enhanced levels of the GFAP and STAT3 in the IL-6 tg hippocampus compared with the non-tg hippocampus, but no difference for several other proteins. Field potential recordings of synaptic transmission at the Schaffer collateral to CA1 synapse showed enhanced dendritic excitatory postsynaptic potentials and somatic population spikes in the CA1 region of hippocampal slices from IL-6 tg mice compared with slices from non-tg littermate controls. No differences were observed for several forms of short-term and long-term synaptic plasticity between hippocampal slices from IL-6 tg and non-tg mice. These results demonstrate that elevated levels of IL-6 can alter mechanisms involved in the excitability of hippocampal neurons and synapses, an effect consistent with recent evidence indicating that elevated production of IL-6 plays an important role in conditions associated with seizure activity and in other impairments observed in CNS disorders with a neuroinflammatory component.
登录
查看更多内容
影响因子：
5.5
作者：
Debanne, D;Guerineau, NC;Thompson, SM
通讯作者：
Thompson, SM
影响因子：
2.5
作者：
BELLINGER, FP;MADAMBA, SG;SIGGINS, GR
通讯作者：
SIGGINS, GR
影响因子：
3.2
作者：
Erickson MA;Maramara LA;Lisman J
通讯作者：
Lisman J
影响因子：
2.5
作者：
GADIENT, RA;OTTEN, U
通讯作者：
OTTEN, U
影响因子：
3.6
作者：
De Sarro, G;Russo, E;De Sarro, A
通讯作者：
De Sarro, A