| 19464074 |
Srivareerat M, Tran TT, Salim S, Aleisa AM, Alkadhi KA: Chronic nicotine restores normal Abeta levels and prevents short-term memory and E-LTP impairment in Abeta rat model of Alzheimer's disease. Neurobiol Aging. 2009 May 20.
Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by increased deposition of beta-amyloid (Abeta) peptides and progressive cholinergic dysfunction in regions of the brain involved in learning and memory processing. In AD, progressive accumulation of Abeta peptide impairs nicotinic acetylcholine receptor (nAChR) function by an unknown mechanism believed to involve alpha (7)- and alpha (4) beta (2)-nAChR blockade. The three approaches of the current study evaluated the effects of chronic nicotine treatment in the prevention of Abeta-induced impairment of learning and short-term memory. Rat AD model was induced by 14-day i.c.v. osmotic pump infusion of a 1:1 mixture of 300pmol/day Abeta (1-40)/Abeta (1-42) or Abeta (40-1) (inactive peptide, control). The effect of nicotine (2mg/(kgday)) on Abeta-induced spatial learning and memory impairments was assessed by evaluation of performance in the radial arm water maze (RAWM), in vivo electrophysiological recordings of early-phase long-term potentiation (E-LTP) in urethane-anesthetized rats, and immunoblot analysis to determine changes in the levels of beta-site amyloid precursor protein (APP)-cleaving enzyme (BACE), Abeta and memory-related proteins. The results indicate that 6 weeks of nicotine treatment reduced the levels of Abeta (1-40) and BACE1 peptides in hippocampal area CA1 and prevented Abeta-induced impairment of learning and short-term memory. Chronic nicotine also prevented the Abeta-induced inhibition of basal synaptic transmission and LTP in hippocampal area CA1. Furthermore, chronic nicotine treatment prevented the Abeta-induced reduction of alpha (7)- and alpha (4)-nAChR. These effects of nicotine may be due, at least in part, to upregulation of brain derived neurotropic factor (BDNF). |
162(2,2,2,2) |