Subthalamic Lesion Protects Nigral Dopaminergic Neurons from 6-Hydroxydopamine-induced Cytotoxicity in the Rat Model of Early Parkinson's Disease

ABSTRACT

BACKGROUND: Subthalamic nucleus (STN) activity increases in patients and animal models of Parkinson's disease. It has been proposed that the STN may play a role in the progressive death of nigral dopamine (DA) neurons in PD. We studied the role of the excitatory afferents from the STN in the death of nigral DA neurons after a striatal 6-hydroxy-dopamine (6-OHDA) injection in a 6-OHDA-induced early Parkinson rat model. METHODS: Nigral DA neurons were counted using of tyrosine hydroxylase immunolabeling. Sprague-Dawley rats were subjected to unilateral, ibotenic acid-induced destruction of the STN 3 weeks after producing the early Parkinson model by injecting an intrastriatal 6- OHDA (8.75 microgram). Sham lesions of the STN were made by injecting phosphate-buffered saline. One week after STN ablation, lesions of nigrostriatal DA neurons were induced by repeated intrastriatal injections of 6-OHDA (8.75 microgram). RESULTS: Intrastriatal injections of 6-OHDA caused a progressive loss of nigral tyrosine hydroxylase-positive DA neurons in a dose dependent manner (3.5 microgram, 8.75 microgram, 17.5 microgram). The dose of 8.75 microgram of 6-OHDA was suitable for the early Parkinson model. Previous ablation of the STN significantly attenuated the loss of DA neurons in rats receiving 6-OHDA. Sham lesions of the STN did not affect DA neuron death induced by the toxin. CONCLUSIONS: The results indicate that excitatory inputs from the STN may contribute to the 6-OHDA-induced death of nigral DA neurons in the early state of Parkinson's disease.