Anti-apoptotic effects of valproic acid treatment on dopaminergic neuronal loss in a 6-hydroxydopamine model of Parkinson’s disease in rats

Abstract

Aim: Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons resulting in deterioration of motor activity in patients. Currently, available therapies including Levodopa (L-DOPA) are more geared toward the treatment of symptoms. Therefore, developing effective neuroprotective therapies is needed. Valproic acid (VPA) has shown potent neuroprotective effects on dopamine (DA) neurons in various brain regions. The aim of this study is to investigate whether VPA attenuates the neuronal loss when co-treated with L-DOPA in a 6-hydroxydopamine (6-OHDA) induced PD model in rats. Methods: Male Wistar Albino rats received intranigral injection of 6-OHDA unilaterally. Twelve days later rats received either saline, L-DOPA, VPA, or L-DOPA+ VPA for 9 days. To determine whether rats had dopaminergic neuronal loss apomorphine-induced rotation test was used. Immunohistochemical analyses were performed in the Substantia Nigra pars compacta (SNpc) by measuring the tyrosine hydroxylase (TH) positive neurons and the apoptotic neurons. Results: 6-OHDA injection showed clinically impairment of the motor function with histologically significant damage to the dopaminergic neurons. VPA administration combined with L- DOPA protected neurons in SNpc by increasing the TH positive neurons and by decreasing the apoptotic neurons. L-DOPA given as a monotherapy, on the other hand, was ineffective on these parameters. Conclusion: Our experiments demonstrated that VPA had a neuroprotective effect when used with L-DOPA in the PD rat model.