1570-159X/11 $58.00+.00 ©2011 Bentham Science Publishers Chronic Stress and Alzheimer’s Disease-Like Pathogenesis in a Rat Model: Prevention by Nicotine

Abstract: Environmental factors including chronic stress may play a critical role in the manifestation of Alzheimer’s disease (AD).This review summarizes our studies of the aggravation of the impaired cognitive ability and its cellular and molecular correlates by chronic psychosocial stress and prevention by nicotine in an A rat model of AD. We utilized three approaches: learning and memory tests in the radial arm water maze, electrophysiological recordings of the cellular correlates of memory, long-term potentiation (LTP) and long-term depression (LTD), in anesthetized rats, and immunoblot analysis of synaptic plasticity- and cognition-related signaling molecules. The A rat model, representing the sporadic form of established AD, was induced by continuous i.c.v. infusion of a pathogenic dose of A peptides via a 14-day osmotic pump. In this AD model, chronic stress intensified cognitive deficits, accentuated the disruption of signaling molecules levels and produced greater depression of LTP than what was seen with A infusion alone. Chronic treatment with nicotine was highly efficient in preventing the effects of A infusion and the exacerbating impact of chronic stress. Possible mechanisms for the effect of chronic stress are discussed