The effects of valproic acid on motor impairment, oxidative stress parameters, apoptotic markers and epigenetic mechanisms in a 6-hydroxydopamine rat model of Parkinson's disease

Parkinson's Disease (PD) is characterized by the progressive loss of dopaminergic neurons resulting in deteriorated motor activity in patients. Currently, there is only symptomatic treatment; therefore, developing effective neuroprotective and neurorestorative therapies is needed. Studies indicate neuroprotective effects of histone deacetylase inhibition in PD models. Valproic acid (VPA), which is used in the treatment of epilepsy, is a histone deacetylase inhibitor and there is limited information on the effects of VPA in PD. The aim of this study is to use VPA post-acutely and compare its potential effects on neuronal survival, motor activity, oxidative stress parameters, apoptotic mechanisms and histone acetylation levels in the brain with the effects of gold standard therapeutic agent levodopa in a 6-hydroxydopamine animal model of PD. The results of this study demonstrated that VPA treatment decreased the number of apoptotic neurons and slightly increased the number of dopaminergic neurons. VPA treatment reduced oxidative stress by decreasing the level of malondialdehyde and increasing the activities of superoxide dismutase, glutathione S-transferase and reduced glutathione. The phosphorylation of both p90RSK and ribosomal S6 protein, which are involved in cell survival and proliferation process, are increased in VPA treated groups. Furthermore, histone acetylation was slightly increased in VPA treated groups. Although the locomotor activity parameters were slightly improved, they were still lower than sham operated groups. Over all, these results indicate that VPA may have therapeutic potential in the treatment of PD, but further research should be performed in order to fully understand its limitations and potential therapeutic effects.