SIRT1 activation by resveratrol reverses atrophy of apical dendrites of hippocampal CA1 pyramidal neurons and neurobehavioral impairments in moderate grade hepatic encephalopathy rats

Abstract

A preliminary observation about resveratrol (RSV) dependent normalization of inflammatory and apoptotic factors in the cortex of hyperammonemic rat model of moderate grade hepatic encephalopathy (MoHE) led us to evaluate whether RSV is ultimately able to confer neuroprotection against MoHE pathogenesis and that it does so by activating its bonafide molecular target SIRT1. The present study compared the profile of relevant neurobehavioral pattern vs neuromorphometry of hippocampal CA1 neurons and SIRT1 activity in the hippocampus of the chronic liver failure (CLF) model of moderate grade HE (MoHE) rats induced by administration of 100 mg/kg body weight of thioacetamide i.p. for 10 days and in the CLF/MoHE rats treated with 10 mg/kg body weight RSV i.p. for 7 days. As compared to the control group rats, the MoHE rats showed significantly deranged pattern of memory and motor functions on MWM and rota rod tests, respectively. These behavioural deficits were associated with a significant reduction in apical dendrite length and number of branching points in the CA1 pyramidal neurons. Interestingly, all these parameters were found to be recovered back to their normal levels in the MoHE rats treated with RSV. Concordantly, MoHE associated declined SIRT1 activity in the hippocampus could be normalized back due to RSV treatment to those MoHE rats. Our findings suggest that RSV is able to normalize MoHE associated memory impairments and motor deficits vis a vis reversal of CA1 dendritic atrophy via SIRT1 activation.