Demyelination-Induced Inflammation Attracts Newly Born Neurons to the White Matter
Demyelination-Induced Inflammation Attracts Newly Born Neurons to the White Matter
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DOI：
10.1007/s12035-016-0127-5
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发表时间：
2017-10-01
影响因子：
5.1
通讯作者：
Mouihate, Abdeslam
中科院分区：
文献类型：
--
作者：
Kalakh, Samah;Mouihate, Abdeslam
有令人信服的证据表明，小胶质细胞活化对神经发生产生负面影响。然而，小胶质细胞也被证明可以促进新生神经元向灰质受损区域的募集。在本研究中，我们探讨了脱髓鞘引发的炎症是否改变了白色物质中的神经发生过程。将2 μ l 0.04%溴化乙锭溶液立体定位注射到成年雄性大鼠的胼胝体中。通过每日注射孕酮（5 mg/kg，s.c.）14天。对照大鼠接受油（s.c.）。使用免疫荧光染色在脱髓鞘位点附近监测新生神经元（DCX和Tbr 2）、小胶质细胞（Iba-1）、星形胶质细胞（波形蛋白或GFAP）、少突胶质细胞祖细胞（OPC; NG 2）和成熟少突胶质细胞（CC-1）。Western blot检测小胶质细胞M1（iNOS）和M2（iNOS-1）的分化情况。局灶性脱髓鞘引起强烈的小胶质细胞和星形胶质细胞活化，并减少脱髓鞘部位的OPC数量。这种炎症反应与白色物质和脑室下区（SVZ）新生神经元数量增加有关。在白色物质中新生神经元的比例显示出OPCs的特征。有趣的是，钝化的脑炎症导致脱髓鞘区域周围和SVZ中的神经发生减少。这些数据表明，白色物质炎症为新生神经元的募集创造了有利的环境。这些新生神经元中有相当一部分采用OPC特征，这表明它们可能有助于髓鞘再生过程。
There is compelling evidence that microglial activation negatively impacts neurogenesis. However, microglia have also been shown to promote recruitment of newly born neurons to injured areas of the gray matter. In the present study, we explored whether demyelination-triggered inflammation alters the process of neurogenesis in the white matter. A 2-mu l solution of 0.04 % ethidium bromide was stereotaxically injected into the corpus callosum of adult male rats. Brain inflammation was dampened by daily injections of progesterone (5 mg/kg, s.c.) for 14 days. Control rats received oil (s.c.). Newly born neurons (DCX and Tbr2), microglia (Iba-1), astrocytes (vimentin or GFAP), oligodendrocyte progenitor cells (OPCs; NG2), and mature oligodendrocytes (CC-1) were monitored in the vicinity of demyelination site using immunofluorescent staining. Western blot was used to explore microglial polarization using M1 (iNOS) and M2 (arginase-1) markers. Focal demyelination elicited strong microglial and astroglial activation and reduced the number of OPCs at the site of demyelination. This inflammatory response was associated with enhanced number of newly born neurons in the white matter and the subventricular zone (SVZ). A proportion of newly born neurons within the white matter showed features of OPCs. Interestingly, blunting brain inflammation led to reduced neurogenesis around the demyelination area and in the SVZ. These data suggest that the white matter inflammation creates a conducive environment for the recruitment of newly born neurons. The fact that a sizable fraction of these newly born neurons adopt OPC features suggests that they could contribute to the remyelination process.