Cytotoxic Effect of 6-OHDA on the Dopaminergic Neurons and Astrocytes in the Dorsal Raphe Nucleus of the Rat

Hong, Eun Seog; Nam, Seong Ahn; Jo, Seung Mook; Kang, Tae Cheon; Won, Moo Ho; Choi, Chang Do

Abstract

This study was designed to clarify the cytotoxic effects of 6-hydroxydopamine (6-OHDA) on the dopaminergic neurons and astrocytes in the dorsal raphe nucleus (DRN), and to investigate neurodegenerative changes by immuno-histochemistry. Adult male rats (Sprague-Dawley strain) weighing from 250 to 350 g were used as experimental animals. 6-OHDA (100 micrometer dissolved in 0.1% ascorbic acid) was injected into the lateral ventricle of the rat brain with the Hamilton syringe. The control rats were treated with the similar volume of 0.1 % ascorbic acid. The rats were sacrificed at the 3rd, 5th, 10th and 20th day, respectively, after the injection of 6-OHDA. The cytotoxicity of 6-OHDA resulted in severe neurodegeneration of the dopaminergic neurons in the DRN. In the 3rd day, the dopaminergic fibers were dilated. In the 5th and 10th days, the dopaminergic fibers were depleted, and dopaminergic cell bodies were shrunken. In the 20th day, the dopaminergic cell bodies were almost completely disappeared. Astroglial reactions induced by 6-OHDA were also observed in the DRN. In the 5th day, astrocytes were significantly increased as compared with that of the control value. The value were reached at its maximum by the 20th day. Based on the present results, it suggests that 6-OHDA may act as a specific neurotoxin to dopaminergic neurons in the DRN, and induce severe neurodegenerative changes. Also, it suggests that the astroglial reaction in the DRN is gradually activated during the neurodegerative changes.