Glioprotective Effect of Resveratrol: an Emerging Therapeutic Role for Oligodendroglial Cells.

Resveratrol is a natural polyphenol compound highly found in red wine that displays several beneficial effects on the central nervous system (CNS), preventing or slowing the progression of a wide variety of neurological diseases. Its neuroprotective role is particularly associated to modulation of antioxidant and anti-inflammatory responses in glial cells in a mechanism dependent of heme oxygenase 1 (HO-1) signaling pathway. Oligodendrocyte progenitor cells (OPC), primarily known for giving rise to mature oligodendrocytes, have emerged as dynamic cells that are also important to maintain the CNS homeostasis. In this sense, we have demonstrated that resveratrol has a protective effect on oligodendroglial functionality against lipopolysaccharide (LPS)-mediated cytotoxicity and that its glioprotective mechanism involves the nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 pathways. LPS, through toll-like receptor 4 (TLR4), affected the release of trophic factors by OPC, including transforming growth factor beta (TGF-β), brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF), and resveratrol reestablished the trophic factor release to control levels. Additionally, resveratrol prevented the LPS-induced increase in the intracellular reactive oxygen species (ROS) as well as the decrease in glutathione (GSH) levels and in glutamate cysteine ligase (GCL) activity, through Nrf2/HO-1 signaling pathways. Resveratrol also prevented the increase of the transcriptional activities of nuclear factor κB (NFκB) and hypoxia-inducible factor 1 alpha (HIF-1α) after LPS challenge. In summary, this is the first study showing the glioprotective effect of resveratrol on oligodendroglial cells.