科研之友
微信
新浪微博
Facebook
分享链接
摘要
Amyloid beta protein (A beta) 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 alpha 4 beta 2 subtype nAChRs, are involved in A beta-induced impairment of hippocampal LTP. The present study investigates a possible role of nAChRs during the impairment of LTP by A beta. Our results showed that: (1) intracerebroventricular injection of A beta(1-40), A beta(25-35) or A beta(31-35) significantly suppressed high-frequency stimulation-induced LTP, while A beta(35-31), a reversed sequence of A beta(31-35), have no effect on the LTP: (2) epibatidine, a specific agonist of alpha 4 beta 2 subtype of nAChRs, dose-dependently suppressed the induction of LTP; (3) co-injection of epibatidine together with A beta(31-35) did not further enhance the suppression of LTP induced by A beta(31-35) or epibatidine alone; (4) dihydro-beta-erythroidine, a selective antagonist against alpha 4 beta 2 subtype of nAChRs, showed no effect on the induction of LTP, but significantly reversed A beta(31-35)-induced LTP impairment. These results indicate that: (1) sequence 31-35 in A beta molecule might be a shorter active center responsible for the neurotoxicity of full length of A beta; (2) alpha 4 beta 2 subtype of nAChRs is required for the suppressive action of A beta on the hippocampal LTP in vivo. Thus, the present study provides further insight into the mechanisms by which A beta impairs synaptic plasticity and cognitive function in the AD brain.
- 出版日期2008-9-30
- 单位山西医科大学
