Parkinson's disease (PD) is caused by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to strong motor impairments. Dopaminergic neurons from the SNc project to the striatum which allow the control of voluntary movements. Vitamin A, through the action of its active metabolite, retinoic acid (RA), is involved in the development, differentiation and neuroprotection of SNc dopaminergic neurons. Additionally, retinaldehyde dehydrogenase (RALDH), the synthesis enzyme of retinoic acid, is involved in cellular detoxification. However, the cerebral bioavailability of retinoic acid decreases with aging, which downregulates RALDH expression. This may precipitate neurodegenerative processes such as those observed in Parkinson's disease. Here we hypothesize that nutritional supplementation with vitamin A normalizes brain levels of retinoic acid and thus RALDH, which exhibit a neuroprotective effect on dopaminergic neurons, to delay the progression of the disease. To test our hypothesis, we modeled Parkinson's disease with unilateral injection of 6-hydroxydopamine (6-OHDA), a toxin that selectively destroys dopaminergic neurons, into rats' striatum. Rats were supplemented or not with dietary vitamin A (20 UI/g) for 5 weeks before the lesion. Motor impairments induced by 6-OHDA and protective effect of vitamin A were quantified with the step test, cylinder test and rotarod. Extend of dopaminergic neurons degeneration was assessed with stereological analysis of tyrosine hydroxylase, the production enzyme of dopamine, staining in the striatum. To evaluate the functionality of the dopaminergic system, levels of dopamine and its metabolites were measured in the striatum with HPLC. Finally, to precisely interrogate the impact of vitamin A supplementation on RALDH enzyme, its expression and localization will be assessed with immunostaining, western blot and RT-qPCR analyses. These experiments that are still in progress will allow a precise assessment of the neuroprotective effects of vitamin A supplementation on dopaminergic neurons in a rat model of Parkinson's disease. This work may open therapeutic strategies to prevent neurodegeneration.< Leer menos