The Behavioral Changes and the Patterns of Dopamine NeuronalDegeneration after Intrastriatal 6-hydroxydopamine Injection in Rat

J Korean Neurol Assoc > Volume 18(6); 2000 > Article

Journal of the Korean Neurological Association 2000;18(6): 741-747.

6-hydroxydopamine을 흰쥐 줄무늬체에 투여한 파킨슨병 모델의 행동학적 특성 및 도파민 신경세포의 퇴행 양상

이원용, 김경문 ·이정일*

성균관대학 의과대학 삼성서울병원 신경과학교실,신경외과*

The Behavioral Changes and the Patterns of Dopamine NeuronalDegeneration after Intrastriatal 6-hydroxydopamine Injection in Rat

Won Yong Lee, M.D. Gyeong-Moon Kim, M.D., Jung-Il Lee, M.D.*

Department of Neurology & Neurosurgery*, Samsung Medical Center, Sungkyunkwan University School of Medicine

Abstract

Background : The terminal destruction of the striatal dopaminergic axon can produce the retrograde degeneration of nigral dopaminergic neurons. An analyses of the postsynaptic dopamine D1 & D2 receptors and the DOPAC/DA level, revealed that this model mimics the early course of Parkinson’s disease in humans. We evaluated the time course of the retrograde dopaminergic neuronal degeneration and the pattern of dopaminergic neuronal loss in the substantia nigra after various doses of 6-hydroxydopamine (6-OHDA) injections in the striatum of rats. Methods : Different doses of 6- OHDA (0.0, 1.25, 2.5, 5, 10 ug/ul in 3.5 ul of saline) were unilaterally injected into the right striatum of rats using a stereotaxic frame. Structural and functional deficits were quantified and compared using apomorphine-induced rotations and tyrosine hydroxylase-immunoreactive (TH-IR) cell numbers in the substantia nigra pars compacta (SNpc) at 3, 6, 9 weeks after lesioning. Results : Striatal 6-OHDA lesions produced dose-dependent decreases in TH-IR cell numbers in SNpc at 3 weeks (-3.8%, 17.9%, 41.2%, 58.5%, 69.9% cell loss compared with the contralesional side respectively), where the ventrolateral portion of the SNpc were more affected. As time progressed, nigral cell loss was significantly increased in all dosage groups and the lesion extended to the medial side of the SNpc and the ventral tegmental area. Apomorphine-induced rotations did not correlate well with nigral TH-IR cell loss. Conclusions : Intrastriatal injections of 6-OHDA, results in time-dependent and dose-dependent progressive degeneration of nigral dopaminergic neurons. We conclude that this rat model can be useful for the evaluation of further neuroprotective and neurotrophic therapies. J Korean Neurol Assoc 18(6):741~747, 2000Key Words : Parkinson’s disease, Cell death, 6-hydroxydopamine, Intrastriatal injection, Apomorphine-induced rota-tion, Apoptosis