Document Detail


Alpha4beta2 nicotinic acetylcholine receptors are required for the amyloid beta protein-induced suppression of long-term potentiation in rat hippocampal CA1 region in vivo.
MedLine Citation:
PMID:  18602971     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Amyloid beta protein (Abeta) is thought to be responsible for the deficit of learning and memory in Alzheimer's disease (AD), possibly through interfering with synaptic plasticity such as hippocampal long-term potentiation (LTP). Nicotinic acetylcholine receptors (nAChRs) participate in various cognitive brain functions. However, it is unclear whether nAChRs, especially alpha4beta2 subtype nAChRs, are involved in Abeta-induced impairment of hippocampal LTP. The present study investigates a possible role of nAChRs during the impairment of LTP by Abeta. Our results showed that: (1) intracerebroventricular injection of Abeta(1-40), Abeta(25-35) or Abeta(31-35) significantly suppressed high-frequency stimulation-induced LTP, while Abeta(35-31), a reversed sequence of Abeta(31-35), have no effect on the LTP; (2) epibatidine, a specific agonist of alpha4beta2 subtype of nAChRs, dose-dependently suppressed the induction of LTP; (3) co-injection of epibatidine together with Abeta(31-35) did not further enhance the suppression of LTP induced by Abeta(31-35) or epibatidine alone; (4) dihydro-beta-erythroidine, a selective antagonist against alpha4beta2 subtype of nAChRs, showed no effect on the induction of LTP, but significantly reversed Abeta(31-35)-induced LTP impairment. These results indicate that: (1) sequence 31-35 in Abeta molecule might be a shorter active center responsible for the neurotoxicity of full length of Abeta; (2) alpha4beta2 subtype of nAChRs is required for the suppressive action of Abeta on the hippocampal LTP in vivo. Thus, the present study provides further insight into the mechanisms by which Abeta impairs synaptic plasticity and cognitive function in the AD brain.
Authors:
M N Wu; Y X He; F Guo; J S Qi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-09
Journal Detail:
Title:  Brain research bulletin     Volume:  77     ISSN:  1873-2747     ISO Abbreviation:  Brain Res. Bull.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-25     Completed Date:  2008-10-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7605818     Medline TA:  Brain Res Bull     Country:  United States    
Other Details:
Languages:  eng     Pagination:  84-90     Citation Subset:  IM    
Affiliation:
Department of Neurobiology and the national key discipline of physiology, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
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MeSH Terms
Descriptor/Qualifier:
Amyloid beta-Protein / administration & dosage,  genetics,  pharmacology*
Animals
Bicyclo Compounds, Heterocyclic
Dihydro-beta-Erythroidine / pharmacology
Electrophysiology
Excitatory Postsynaptic Potentials / drug effects,  physiology
Hippocampus* / anatomy & histology,  drug effects,  physiology
Humans
Long-Term Potentiation / drug effects*,  physiology
Male
Neuronal Plasticity / drug effects,  physiology
Nicotinic Agonists / pharmacology
Peptide Fragments / administration & dosage,  genetics,  pharmacology*
Pyridines
Rats
Rats, Wistar
Receptors, Nicotinic / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Amyloid beta-Protein; 0/Bicyclo Compounds, Heterocyclic; 0/Nicotinic Agonists; 0/Peptide Fragments; 0/Pyridines; 0/Receptors, Nicotinic; 0/amyloid beta-protein (1-40); 0/amyloid beta-protein (25-35); 0/amyloid beta-protein (31-35); 0/nicotinic receptor alpha4beta2; 140111-52-0/epibatidine; 23255-54-1/Dihydro-beta-Erythroidine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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