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通过经典的 IKK/NF-κB 信号通路,TNF-α 诱导的小鼠脑炎症在区域上具有易感性。

Regional susceptibility to TNF-α induction of murine brain inflammation via classical IKK/NF-κB signalling.

机构信息

School of Medicine, University of St. Andrews, Fife, Scotland, United Kingdom.

出版信息

PLoS One. 2012;7(6):e39049. doi: 10.1371/journal.pone.0039049. Epub 2012 Jun 11.

Abstract

It is becoming clear that inflammation plays a significant role in a number of neurological and psychiatric conditions. Post mortem brain samples in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, schizophrenia and most recently autism spectrum condition, all exhibit neuroglial activation and inflammatory markers within the CSF. Many questions remain about the underlying molecular mechanisms. By adding the pro-inflammatory cytokine, TNF-α, to mouse brain tissue we demonstrated that the frontal lobes and temporal region, areas involved in higher functions such as memory and learning, are most susceptible to cytokine-induced inflammation via the NF-κB signalling pathway. We observed direct correlations between the volumetric increase and molecular expression indicating that therapeutic targets in these lobes may require different approaches when treating conditions with a central neuroinflammatory component.

摘要

很明显,炎症在许多神经和精神疾病中起着重要作用。阿尔茨海默病、帕金森病、肌萎缩性侧索硬化症、多发性硬化症、精神分裂症,以及最近的自闭症谱系障碍的死后大脑样本都表现出神经胶质激活和脑脊液中的炎症标志物。关于潜在的分子机制仍有许多问题有待解答。通过向小鼠脑组织中添加促炎细胞因子 TNF-α,我们证明了额叶和颞叶(参与记忆和学习等高级功能的区域)最容易受到 NF-κB 信号通路引起的细胞因子诱导的炎症的影响。我们观察到体积增加和分子表达之间存在直接相关性,表明在治疗具有中枢神经炎症成分的疾病时,这些脑叶的治疗靶点可能需要采用不同的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9e6/3372464/2607c60fd2fb/pone.0039049.g001.jpg

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