Allergy Enhances Neurogenesis and Modulates Microglial Activation in the Hippocampus.
Allergy Enhances Neurogenesis and Modulates Microglial Activation in the Hippocampus.
复制标题
DOI：
10.3389/fncel.2016.00169
复制
发表时间：
2016
影响因子：
5.3
通讯作者：
Aigner L
中科院分区：
文献类型：
--
作者：
Klein B;Mrowetz H;Thalhamer J;Scheiblhofer S;Weiss R;Aigner L
过敏及其特有的 TH2 极化炎症反应影响着很大一部分人群。由于越来越多的证据表明免疫系统调节中枢神经系统 (CNS) 的可塑性和功能，我们研究了过敏性肺部炎症对海马体（成人大脑中细胞可塑性区域）的影响。本研究的重点是小胶质细胞（中枢神经系统的常驻免疫细胞）和海马神经发生（即新神经元的生成）。 C57BL/6 小鼠用源自梯牧草花粉 (Phl p 5) 的临床相关过敏原致敏。正如预期的那样，过敏致敏导致过敏原特异性免疫球蛋白（IgG1 和 IgE）和 TH2 细胞因子（IL-5 和 IL-13）血清水平升高。令人惊讶的是，在海马齿状回的颗粒层（GL）和颗粒下区（SGZ）中发现了较少的Iba1+小胶质细胞，并且Iba1+MHCII+细胞的数量也较低，表明过敏小鼠海马中的小胶质细胞监视和激活减少。通过用溴脱氧尿苷 (BrdU) 标记增殖细胞并在 4 周后确定其命运来分析神经发生，并通过对年轻的未成熟神经元（即表达双皮质素 (DCX) 的细胞）进行定量分析。过敏动物中DCX+细胞的数量明显增加。此外，过敏小鼠的海马体中存在更多的 BrdU+ 细胞，并且这些新生细胞已分化为神经元，大量 BrdU+NeuN+ 细胞表明这些新生细胞已分化为神经元。总之，过敏导致小胶质细胞的存在和活性减少，并导致海马神经发生水平升高。这种效应显然是海马体特有的，因为我们没有在室下区（SVZ）/嗅球（OB）系统中观察到这些变化，该系统也是一个具有高细胞可塑性和成人神经发生的区域。
Allergies and their characteristic TH2-polarized inflammatory reactions affect a substantial part of the population. Since there is increasing evidence that the immune system modulates plasticity and function of the central nervous system (CNS), we investigated the effects of allergic lung inflammation on the hippocampus—a region of cellular plasticity in the adult brain. The focus of the present study was on microglia, the resident immune cells of the CNS, and on hippocampal neurogenesis, i.e., the generation of new neurons. C57BL/6 mice were sensitized with a clinically relevant allergen derived from timothy grass pollen (Phl p 5). As expected, allergic sensitization induced high serum levels of allergen-specific immunoglobulins (IgG1 and IgE) and of TH2 cytokines (IL-5 and IL-13). Surprisingly, fewer Iba1+ microglia were found in the granular layer (GL) and subgranular zone (SGZ) of the hippocampal dentate gyrus and also the number of Iba1+MHCII+ cells was lower, indicating a reduced microglial surveillance and activation in the hippocampus of allergic mice. Neurogenesis was analyzed by labeling of proliferating cells with bromodeoxyuridine (BrdU) and determining their fate 4 weeks later, and by quantitative analysis of young immature neurons, i.e., cells expressing doublecortin (DCX). The number of DCX+ cells was clearly increased in the allergy animals. Moreover, there were more BrdU+ cells present in the hippocampus of allergic mice, and these newly born cells had differentiated into neurons as indicated by a higher number of BrdU+NeuN+ cells. In summary, allergy led to a reduced microglia presence and activity and to an elevated level of neurogenesis in the hippocampus. This effect was apparently specific to the hippocampus, as we did not observe these alterations in the subventricular zone (SVZ)/olfactory bulb (OB) system, also a region of high cellular plasticity and adult neurogenesis.