title: Chronic psychosocial stress exacerbates impairment of synaptic plasticity in β-amyloid rat model of Alzheimer's disease: prevention by nicotine.
abstract: Alzheimer's 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.
authors: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA. kalkadhi@uh.edu
authors: Karim A
authors: KA
authors: Alkadhi
authors: Karem H
authors: KH
authors: Alzoubi
authors: Marisa
authors: M
authors: Srivareerat
authors: Trinh T
authors: TT
authors: Tran
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000150:complications*
chemical_list: D016229:Amyloid beta-Peptides; D018722:Nicotinic Agonists; D009538:Nicotine