title: Intensification of long-term memory deficit by chronic stress and prevention by nicotine in a rat model of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cholinergic dysfunction and deposition of beta-amyloid (Aβ) in regions of the brain associated with learning and memory. The sporadic nature and late onset of most AD cases suggests that aside from biological determinants, environmental factors such as stress may also play a role in the progression of the disease. Behavioral and molecular studies were utilized to evaluate the effects of chronic nicotine treatment in the prevention of impairment of long-term memory. The rat model of AD was induced by i.c.v. osmotic pump infusion of Aβ peptides. Chronic psychosocial stress and chronic nicotine treatment were instituted for 6weeks. Spatial memory testing in the Radial Arm Water Maze revealed that, although stress, by itself, did not affect long-term memory, the combination of chronic stress and Aβ infusion impaired long-term memory significantly more than Aβ peptides infusion alone. Chronic nicotine treatment completely prevented Aβ- and stress/Aβ combination-induced memory impairment. Furthermore, molecular findings in hippocampal CA1 region of stress/Aβ rats indicated marked reduction in the protein levels of phosphorylated cAMP response element binding (p-CREB) and calcium-calmodulin-dependent protein kinase IV (CaMKIV), with significant increases in the levels of brain-derived neurotrophic factor (BDNF). These disturbances in signaling pathways, which may be the underlying mechanisms of impairment of long-term memory in these rats, were totally prevented by chronic nicotine treatment.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204-5037, USA. kalkadhi@uh.edu
authors.forename: Karim A
authors.initials: KA
authors.lastname: Alkadhi
authors.forename: Marisa
authors.initials: M
authors.lastname: Srivareerat
authors.forename: Trinh T
authors.initials: TT
authors.lastname: Tran
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology*; D000682:Amyloid / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005731:Ganglionic Stimulants / Q000494:pharmacology / Q000627:therapeutic use; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000503:physiopathology; D057567:Memory, Long-Term / Q000187:drug effects* / Q000502:physiology; D009483:Neuropsychological Tests; D009538:Nicotine / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology
chemical_list: D000682:Amyloid; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D005731:Ganglionic Stimulants; D009538:Nicotine; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4