Valproic acid neuroprotection in 6-OHDAlesioned rat, a model for parkinson's disease

Background: Valproic acid (VPA) a long standing anti-epileptic and anti-manic drug has been recently investigated as a neuroprotective molecule, in relation to its action as an inhibitor of histone deacetylases (HDACs), favoring relaxed configuration of chromatin and thus promoting gene transcription. Methods: In the present study, chronic administration of VPA added to the diet, was tested for neuroprotection in a rat model of Parkinson's disease. The model consists of multiple injections of the dopaminergic toxin, 6-hydroxydopamine (6-OHDA), unilaterally in the striatum with consequent degeneration of the dopaminergic neurons originating the nigro-striatal pathway. This model of neurodegeneration is widely used as a reliable animal model for Parkinson's disease (PD). Results: Chronic VPA administration significantly reduced degeneration of dopaminergic neurons in the substantia nigra, and of dopaminergic terminals in the striatum, in rats subjected to the unilateral lesion of the nigrostriatal pathway. VPA treatment was also able to increase α-synuclein expression in the substantia nigra and to counteract the lesion-dependent decrease of the protein in the substantia nigra itself and in the striatum. Conclusions: Present data, which follow previous results obtained in the rotenone rat model of nigrostriatal degeneration, allow to propose VPA as a treatment to be tested for its effectiveness in other animal models of parkinsonism, in view of possible translation to patients.