Goings Gwendolyn E, Greisman Adriana, James Rachel E, Abram Leanne Kf, Begolka Wendy Smith, Miller Stephen D, Szele Francis G
Department of Physiology, Anatomy, and Genetics, Oxford University, UK.
J Neuroinflammation. 2008 Oct 15;5:44. doi: 10.1186/1742-2094-5-44.
The periventricular subventricular zone (SVZ) contains stem cells and is an area of active neurogenesis and migration. Since inflammation can reduce neurogenesis, we tested whether Theiler's murine encephalomyelitis virus (TMEV) induces inflammation and reduces neurogenesis in the SVZ.
We performed immmunohistochemistry for the hematopoietic cell marker CD45 throughout the central nervous system and then examined neuroblasts in the SVZ.
CD45+ activation (inflammation) occurred early in the forebrain and preceded cerebellar and spinal cord inflammation. Inflammation in the brain was regionally stochastic except for the SVZ and surrounding periventricular regions where it was remarkably pronounced and consistent. In preclinical mice, SVZ neuroblasts emigrated into inflamed periventricular regions. The number of proliferating phoshpohistone3+ cells and Doublecortin+ (Dcx) SVZ neuroblasts was overall unaffected during the periods of greatest inflammation. However the number of Dcx+ and polysialylated neural cell adhesion molecule (PSA-NCAM+) SVZ neuroblasts decreased only after periventricular inflammation abated.
Our results suggest that after TMEV infection, the SVZ may mount an attempt at neuronal repair via emigration, a process dampened by decreases in neuroblast numbers.
脑室周围室下区(SVZ)含有干细胞,是神经发生和迁移活跃的区域。由于炎症会减少神经发生,我们测试了泰勒氏鼠脑脊髓炎病毒(TMEV)是否会诱发炎症并减少SVZ中的神经发生。
我们在整个中枢神经系统中对造血细胞标志物CD45进行免疫组织化学检测,然后检查SVZ中的神经母细胞。
CD45+激活(炎症)在前脑早期发生,先于小脑和脊髓炎症。除SVZ及其周围脑室周围区域炎症明显且一致外,脑内炎症在区域上是随机的。在临床前小鼠中,SVZ神经母细胞迁移到发炎的脑室周围区域。在炎症最严重的时期,增殖的磷酸化组蛋白3+细胞和双皮质素+(Dcx)SVZ神经母细胞的数量总体上未受影响。然而,只有在脑室周围炎症消退后,Dcx+和多唾液酸神经细胞黏附分子(PSA-NCAM+)SVZ神经母细胞的数量才会减少。
我们的结果表明,TMEV感染后,SVZ可能会通过迁移进行神经元修复尝试,这一过程会因神经母细胞数量减少而受到抑制。