The study of physiological and pathophysiological functions of glial cells mediated by neuro-immuno interaction

为了探讨神经免疫相互作用可能介导的神经胶质细胞的生理和病理生理功能，研究了神经胶质细胞系衍生物质在神经元损伤中的作用。胶质细胞系衍生神经营养因子是一种强有力的神经营养因子，具有多种生物活性，可影响中枢和外周神经系统中的多种神经元。在本研究中，我们观察了GDNF对大鼠短暂性前脑缺血后海马CA1区迟发性神经元死亡的影响。海马区直接微量注射GDNF1.0μg对延迟性海马神经元死亡有明显的保护作用。此外，DNA片段化原位染色显示，GDNF对脑缺血诱导的海马区CA1区细胞凋亡有明显的保护作用。这些发现表明gdnf在…中起着重要的作用。在脑缺血诱导的迟发性神经元死亡中有更多的OLE。在下一系列中，我们研究了GDNF保护迟发性神经元死亡的可能机制。已有研究表明，多巴胺(DA)在神经元培养中触发细胞凋亡，在短暂性前脑缺血后，DA被过量释放到海马区。短暂性前脑缺血后，海马区酪氨酸羟化酶(TH)基因和蛋白表达增加。相反，海马区多巴胺β-羟基酶的基因和蛋白没有增加。有趣的是，海马区微量注射GDNF1.0μg可降低海马区THmRNA和TH样免疫组织化学阳性终末的诱导水平。而正常大鼠局部应用GDNF后，TH基因表达增加。这些发现表明，GDNF可部分通过调节TH基因和蛋白的表达水平来保护海马CA1区神经元的变性，包括延迟性神经元死亡。较少

To investigate a possible physiological and pathophysiological functions of glial cells mediated by neuro-immuno interaction, role of glial cell line derived substances on neuronal damage was studied.Glial cell line-derived neurotrophic factor (GDNP) is a potent neurotrophic factor, which has a variety of biological activities that affect several types of neurons in both the central and peripheral nervous systems. In this study, we examined the effects of GDNF on delayed neuronal death in the hippocampal CA1 region of rats after transient forebrain ischemia. Pretreatment with GDNF (1.0 μg), which was directly microinjected into the hippocampal CA1 region, gave significant protection against the delayed hippocampal neuronal death. In addition, pretreatment with GDNF gave significant protection against apoptotic cell death induced by brain ischemia in the hippocampal CA1 region, as determined by in situ staining for DNA fragmentation. These findings suggest that GDNF plays an important r … More ole in delayed neuronal death induced by brain ischemia.In the next series, possible mechanisms of GDNF to protect the delayed neuronal death were studied. It has been shown that dopamine (DA) triggers apoptosis in neuronal cultures and that DA is released in excessive amounts into the hippocampus following transient forebrain ischemia. The expression of tyrosine hydroxylase (TH) mRNA and protein was increased in the hippocampus after transient forebrain ischemia. In contrast, no increase in dopamine β-hydroxylase mRNA and protein in the hippocampus was observed. Interestingly, the induction level of TH mRNA and TH like immunohistochemistry positive terminals in the hippocampus were reduced by intrahippocampal microinjection of GDNF (1.0 μg). In contrast, local GDNF-treatment of normal rats increased the TH mRNA expression. These findings suggest that GDNF protects against neuronal degeneration including delayed neuronal death in the hippocampal CA1 region in part by modulating the expression levels of TH mRNA and protein . Less