Resveratrol upregulates sirtuin 1/2, prevents neurotoxicity and enhances locomotion after kainate-induced spinal cord injury.

POODTS MARTINA; MAZZONE GL; BENJAMÍN ZYLBERBERG; CORONEL MARIA FLORENCIA; RONCORONI JULIETA

Buenos Aires

Encuentro; SAN meeting; 2022

Sociedad Argentina de Investigación en Neurociencias

Excitotoxicity is a major contributor to the pathophysiology of spinal cord injury (SCI), due to the over-activation of glutamate receptors with important consequences for neuronal death, locomotor function loss and neuropathic pain development. We have shown in our previous studies that 1h kainate application (100M, KA) induced the endogenous release of glutamate and irreversibly suppressed fictive locomotion. Our objective was to evaluate the neuroprotective effects of resveratrol (RESV, 50 mg/kg), a natural polyphenol, after KA-induced SCI, using in vivo and in vitro models. Locomotor behaviors were evaluated in an open field by applying the Basso Mouse locomotor scale rating (BMS), footprinting and horizontal ladder analysis, 1 or 8 days after KA application. RESV co-application with KA demonstrated a significant increase in the BMS score. The histological analysis confirmed that KA reduced the number neurons, while significant neuroprotection was observed after RESV administration in the ventral, central and dorsal spinal regions. Indeed, the application of RESV significant induced sirtuin 1 and 2 expression, evaluated by immunofluorescence, which was dismissed by co-application of KA. Despite the molecular mechanisms of RESV actions need further clarification, our data suggest that excitotoxic damage may be counteracted by RESV, offering a novel perspective for neuroprotective strategies after SCI. Supported by Universidad Austral and CONICET.