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Chronic nicotine restores normal Aβ levels and prevents short-term memory and E-LTP impairment in Aβ rat model of Alzheimer's disease.
- Source :
-
Neurobiology of aging [Neurobiol Aging] 2011 May; Vol. 32 (5), pp. 834-44. Date of Electronic Publication: 2009 May 22. - Publication Year :
- 2011
-
Abstract
- Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by increased deposition of beta-amyloid (Aβ) peptides and progressive cholinergic dysfunction in regions of the brain involved in learning and memory processing. In AD, progressive accumulation of Aβ peptide impairs nicotinic acetylcholine receptor (nAChR) function by an unknown mechanism believed to involve α(7)- and α(4)β(2)-nAChR blockade. The three approaches of the current study evaluated the effects of chronic nicotine treatment in the prevention of Aβ-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 300 pmol/day Aβ(1-40)/Aβ(1-42) or Aβ(40-1) (inactive peptide, control). The effect of nicotine (2 mg/(kg day)) on Aβ-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), Aβ and memory-related proteins. The results indicate that 6 weeks of nicotine treatment reduced the levels of Aβ(1-40) and BACE1 peptides in hippocampal area CA1 and prevented Aβ-induced impairment of learning and short-term memory. Chronic nicotine also prevented the Aβ-induced inhibition of basal synaptic transmission and LTP in hippocampal area CA1. Furthermore, chronic nicotine treatment prevented the Aβ-induced reduction of α(7)- and α(4)-nAChR. These effects of nicotine may be due, at least in part, to upregulation of brain derived neurotropic factor (BDNF).<br /> (Copyright © 2009 Elsevier Inc. All rights reserved.)
- Subjects :
- Amyloid Precursor Protein Secretases metabolism
Animals
Aspartic Acid Endopeptidases metabolism
Brain-Derived Neurotrophic Factor biosynthesis
CA1 Region, Hippocampal drug effects
Disease Models, Animal
Learning drug effects
Male
Maze Learning drug effects
Rats
Rats, Wistar
Receptors, Nicotinic drug effects
Synaptic Transmission drug effects
Up-Regulation
Alzheimer Disease drug therapy
Amyloid beta-Peptides metabolism
Ganglionic Stimulants therapeutic use
Long-Term Potentiation drug effects
Memory Disorders drug therapy
Memory, Short-Term drug effects
Nicotine therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1558-1497
- Volume :
- 32
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Neurobiology of aging
- Publication Type :
- Academic Journal
- Accession number :
- 19464074
- Full Text :
- https://doi.org/10.1016/j.neurobiolaging.2009.04.015