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

BENJAMÍN ZYLBERBERG; MARTINA POODTS; JULIETA RONCORONI; M. FLORENCIA CORONEL

Buenos Aires

Congreso; Congreso Anual SAN 2022; 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 forneuronal death, locomotor function loss and neuropathic pain development. We haveshown in our previous studies that 1h kainate application (100M, KA) induced theendogenous release of glutamate and irreversibly suppressed fictive locomotion. Ourobjective was to evaluate the neuroprotective effects of resveratrol (RESV, 50 mg/kg), anatural polyphenol, after KA-induced SCI, using in vivo and in vitro models.Locomotor behaviors were evaluated in an open field by applying the Basso Mouselocomotor scale rating (BMS), footprinting and horizontal ladder analysis, 1 or 8 daysafter KA application. RESV co-application with KA demonstrated a significant increasein the BMS score. The histological analysis confirmed that KA reduced the numberneurons, while significant neuroprotection was observed after RESV administration inthe ventral, central and dorsal spinal regions. Indeed, the application of RESVsignificant induced sirtuin 1 and 2 expression, evaluated by immunofluorescence, whichwas dismissed by co-application of KA. Despite the molecular mechanisms of RESVactions need further clarification, our data indicate that excitotoxic damage may becounteracted by RESV, offering a novel perspective for neuroprotective strategies afterSCI. Supported by Universidad Austral and CONICET.