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
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