NEUROPROTECTION BY VALPROIC ACID IN AN INTRASTRIATAL ROTENONE MODEL OF PARKINSON′S DISEASE

Rotenone, which is used as a pesticide and ticide, has been shown to cause systemic inhibition of chondrial complex I activity, with consequent of dopaminergic neurons within the substantia nigra striatum, as observed in Parkinson ' s disease. A novel striatal rotenone model of Parkinson ' s disease was used examine the neuroprotective effects of valproic acid (VPA) which is known to upregulate neurotrophic factors other protective proteins in the brain. Sham or lesioned were treated with either vehicle or VPA at a dose of 4 mg/in drinking water. The right striatum was lesioned by sion of rotenone at three sites (2 mu g/site) along its caudal axis. A forelimb asymmetry (cylinder) test a significant (p < 0.01) decrease in use of the forelimb in rotenone-lesioned animals, in the third post-lesioning, which was abolished by VPA treatment. ilarly, a significant (p < 0.01) and persistent increase in of the ipsilateral forelimb in lesioned animals over 4 weeks of testing, was not seen in animals treated VPA. Results of the asymmetry test illustrate that tal infusion of rotenone causes contralateral motor tion, which is blocked by VPA. The significant increase ipsilateral forelimb use has not been previously, and presumably represents a response in lesioned animals. Six weeks post-surgery, mals were sacrificed by transcardial perfusion. immunohistochemical examination revealed a decrease tyrosine hydroxylase immunoreactivity within the and substantia nigra of rotenone-lesioned animals. treatment attenuated the decrease in tyrosine in the striatum and abolished it in the substantia nigra. eological cell counting indicated a significant (p < 0.05) decrease in tyrosine hydroxylase-positive dopamine rons in the substantia nigra of rotenone-lesioned which was confirmed by Nissl staining. Importantly, loss of dopamine neurons in rotenone-lesioned was blocked by chronic VPA treatment. These strongly support the therapeutic potential of VPA Parkinson's disease. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.