The Effect of Intrastriatal 6-Hydroxydopamine injection on the Expression of Neurotrophic factors in the Rat Brain

ABSTRACT

BACKGROUND AND PURPOSE: Neurotrophic factors has been a subject of interest in the research of Parkinson's disease. In this experiment, intrastriatal 6-Hydroxydopamine(6-OHDA) injection was used to observe the effect of dopaminergic deafferentiation on the neurotrophic factor mRNA expression in the rat brain. METHODS: Male Sprague Dawley rats (250~300 gm) were treated to produce specific unilateral dopaminergic deafferentiation via injection of 6-OHDA at the right striatum without effect on the noradrenergic system. Treatment group (N=20) received same volume of vitamin C at the same site. The rats were sacrificed 3 hours, 12 hours, 24 hours, 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, after injection. The expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), tyrosine hydroxylase (TH), and enkephalin (ENK) mRNA were observed by in situ hybridization histochemistry in the hippocampus, striatum and substantia nigra. RESULTS: The expression of BDNF mRNA was increased in the cerebral cortex, dentate gyrus, and hippocampus. In the cerebral cortex, the increase of expression was peaked at 12 hours after 6-OHDA injection and confined to injection side. In the dentate gyrus, the expression was significantly increased in the injection side at 12 hours after injection, after that increased expression was observed in both side. The expression of NGF mRNA was increased in the dentate gyrus and cerebral cortex of lesion side at 3 hours and 12 hours after 6-OHDA injection. However, the expression of NT-3 mRNA was not changed. The expression of TH mRNA was gradually decreased in the substantia nigra compacta of injection side from 1 week to 4 weeks after 6-OHDA injection. The expression of enkephalin mRNA was increased from 24 hours, peaked at 1week, and returned to basal level at 4 weeks after injection in the injection side. CONCLUSION: From this results, it may suggest that the expression of neurotrophic factors in the cerebral cortex, dentate gyrus and hippocampus are closely related with the degeneration of dopaminergic neurons, not with the degeneration of noradrenergic neurons.