Objective: Aim of study was to elucidate the pharmacological Invivo and invitro effects and mechanisms of action of

RT in experimental models of PD.

Background: The MPTP-induced PD model is characterized by chronic inflammation, oxidative stress and loss of the dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Resveratrol (RT) improves cognition and limits neuroinflammation in the brain. However, the beneficial effects of RT in ameliorating Parkinson’s disease (PD) remain unknown.

Method: We utilized SH-SY5Y cells exposed to RT (20μM) against 1-methyl-4-phenylpyridinium iodide (MPP+ ) as an in vitro PD model. Cell viability and apoptosis were analyzed via the MTT assay and flow cytometry. Mitochondrial morphology, apoptotic markers such as B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax), mitochondrial respiratory capacity and ROS were measured by a mitochondrial tracker, a Seahorse analyzer and a MitoSOX-Red dye.

For in vivo PD model, behavioral tests, Nissl staining and immunohistochemistry were used to evaluate the protection of RT (50 mg/kg body weigh). The levels of tyrosine hydroxylase (TH), cAMP response element-binding protein (CREB) and cytokines levels ( IL-1β, IL-6 and TNF-α) were analyzed by by Western blotting, RT-PCR and quantitative PCR analysis.

Results: RT decreased MPP+ -induced apoptosis in SH-SY5Y cells and human dopaminergic neurons. RT also increased mitochondrial respiratory capacity, decreased ROS production and restored mitochondrial morphology. RT reversed the MPP+ -induced reductions of phosphorylated CREB, PGC-1α, and TH, while the protective effects were blocked by the PKA inhibitor H-89 and via PGC-1α siRNA. In mice treated with MPTP, RT significantly improved motor functions. Importantly, RT prevented both dopaminergic neuronal loss and the reduction of phosphorylated CREB and glial activation, decreasing the levels of IL-1β, IL-6 and TNF-α, as well as their respective receptors in the SNpc of MPTP-treated mice.

Conclusion: RT may be a promising neuroprotective agent for the treatment of neurodegenerative disorders such as Parkinson’s disease. Results suggest that RT may play a neuroprotective role via modulating the mitochondrial-mediated signaling and CREB pathway in MPTP/MPP+-induced PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pharmacological-invivo-and-invitro-potential-of-resveratrol-in-experimental-rat-models-of-parkinsons-disease/