Alzheimers disease (AD) is a degenerative disorder that leads to progressive, irreversible cognitive decline. It develops as a result of over-production and aggregation of β-amyloid (Aβ) peptides in the brain. We have recently shown that stress exacerbates, while nicotine prevents long-term memory impairment induced by β-Amyloid. In this study, we evaluated the effect of chronic psychosocial stress on synaptic plasticity (Late-phase long-term potentiation; L-LTP, and long-term depression; LTD) in the β-Amyloid rat model of AD, and the positive impact of chronic nicotine treatment. Chronic psychosocial stress was induced by an intruder method. The Rat AD model was induced by 14-day i.c.v. osmotic pump infusion of a 1:1 mixture of 300 pmol/day Aβ1-40/Aβ1-42. The rats were treated with nicotine (2 mg/kg/day) for 6 weeks. In vivo electrophysiological recordings of L-LTP, and LTD in hippocampal area CA1 showed that chronic stress by itself did not affect L-LTP. However, it markedly aggravated the impairment of this response as well as LTD in Aβ- treated rats. The effects of Aβ and the combination of stress and Aβ were totally prevented by chronic nicotine treatment. Immunoblot analysis revealed that stress and/or Aβ significantly increased the basal levels of calcineurin and prevented the expected L-LTP-induced increase in CREB phosphorylation, and CaMKIV levels. These effects were not seen in Aβ- infused rats chronically treated with nicotine. The changes in synaptic plasticity-related molecules may explain the effects of stress and/or chronic nicotine on L-LTP in Aβ animals.
Keywords: Nicotine, late phase LTP, rat model, Alzheimer's calcineurin, Parkinsons disease, hypothyroidism, long-term depression, chronic psychosocial stress, Abeta administration, postsynaptic potential
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