Oizumi Hideki, Hayashita-Kinoh Hiromi, Hayakawa Hideki, Arai Hiroyuki, Furuya Tsuyoshi, Ren Yong-Ri, Yasuda Toru, Seki Tatsunori, Mizuno Yoshikuni, Mochizuki Hideki
Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan.
Neurosci Res. 2008 Jan;60(1):15-21. doi: 10.1016/j.neures.2007.09.004. Epub 2007 Sep 18.
Enhancement of neurogenesis could be a suitable treatment approach to up-regulate dopaminergic neurons in Parkinson's disease (PD). In the present study, we focused on the kinetics of the subventricular zone (SVZ) in a mouse model of PD induced by MPTP injection. We showed recently the proliferation potential of neuronal stem cells (NSCs) prepared from the olfactory bulb of an animal model of PD [Hayakawa, H., Hayashita-Kinoh, H., Nihira, T., Seki, T., Mizuno, Y., Mochizuki, H., 2007. The isolation of neural stem cells from the OB of Parkinson's disease model. Neurosci. Res.]. In this study, we examined the relationship between proliferation and differentiation of NSCs in SVZ of both acute and chronic PD models. Only acute MPTP treatment significantly increased the areas of glial fibrillary acidic protein (GFAP)-expressing cells and decreased the areas of polysialylated neural cell adhesion molecule (PSA-NCAM)-expressing cells in the SVZ. In the case of caspase-11 knockout mice, MPTP did not induce alteration in the areas of GFAP-expressing cells and PSA-NCAM-expressing cells. Our results suggest that neuroinflammation related to the caspase-11 cascade in the striatum regulates differentiation of neural stem cells in the SVZ of our mouse model of PD.
增强神经发生可能是上调帕金森病(PD)中多巴胺能神经元的一种合适治疗方法。在本研究中,我们聚焦于由MPTP注射诱导的PD小鼠模型中脑室下区(SVZ)的动力学。我们最近展示了从PD动物模型嗅球制备的神经干细胞(NSCs)的增殖潜力[Hayakawa, H., Hayashita-Kinoh, H., Nihira, T., Seki, T., Mizuno, Y., Mochizuki, H., 2007. 从帕金森病模型的嗅球分离神经干细胞。神经科学研究]。在本研究中,我们检查了急性和慢性PD模型中SVZ内神经干细胞增殖与分化之间的关系。仅急性MPTP处理显著增加了SVZ中表达胶质纤维酸性蛋白(GFAP)的细胞面积,并减少了表达多唾液酸神经细胞黏附分子(PSA-NCAM)的细胞面积。在caspase-11基因敲除小鼠中,MPTP并未诱导表达GFAP的细胞面积和表达PSA-NCAM的细胞面积发生改变。我们的结果表明,纹状体中与caspase-11级联相关的神经炎症调节了我们PD小鼠模型SVZ中神经干细胞的分化。