Klein Barbara, Mrowetz Heike, Thalhamer Josef, Scheiblhofer Sandra, Weiss Richard, Aigner Ludwig
Institute of Molecular Regenerative Medicine, Paracelsus Medical UniversitySalzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical UniversitySalzburg, Austria.
Division of Allergy and Immunology, Department of Molecular Biology, University of Salzburg Salzburg, Austria.
Front Cell Neurosci. 2016 Jun 28;10:169. doi: 10.3389/fncel.2016.00169. eCollection 2016.
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.
过敏及其典型的TH2极化炎症反应影响着相当一部分人群。由于越来越多的证据表明免疫系统可调节中枢神经系统（CNS）的可塑性和功能，我们研究了过敏性肺部炎症对海马体（成人大脑中具有细胞可塑性的一个区域）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）和海马体神经发生，即新神经元的生成。用源自梯牧草花粉（Phl p 5）的临床相关过敏原使C57BL/6小鼠致敏。如预期的那样，过敏性致敏诱导了高血清水平的过敏原特异性免疫球蛋白（IgG1和IgE）以及TH2细胞因子（IL-5和IL-13）。令人惊讶的是，在海马齿状回的颗粒层（GL）和颗粒下区（SGZ）中发现的Iba1(+)小胶质细胞较少，并且Iba(+)MHCII(+)细胞的数量也较低，这表明过敏性小鼠海马体中的小胶质细胞监测和激活减少。通过用溴脱氧尿苷（BrdU）标记增殖细胞并在4周后确定它们的命运，以及通过对年轻未成熟神经元（即表达双皮质素（DCX）的细胞）进行定量分析来分析神经发生。在过敏动物中，DCX(+)细胞的数量明显增加。此外，但在过敏性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，这由更多的BrdU(+)NeuN(+)细胞表明。总之，过敏导致海马体中小胶质细胞的存在和活性降低以及神经发生水平升高。这种效应显然对海马体具有特异性，因为我们在脑室下区（SVZ）/嗅球（OB）系统中未观察到这些改变，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。
