期刊
NEUROBIOLOGY OF LEARNING AND MEMORY
卷 91, 期 3, 页码 226-234出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nlm.2008.11.004
关键词
A beta 31-35; A beta 25-35; Late-phase LTP (L-LTP); PKC; Hippocampus; Rats
资金
- National Science Foundation of China [30740095, 30840085]
- Education Ministry Special Foundation for High School's Doctoral Program in China [20060114004]
- Natural Science Foundation of Shanxi Province of China [200601105]
- Natural Science Foundation for Youths of Shanxi Province [2008021045-2]
Amyloid P-protein (A beta) in the brain of Alzheimer's disease (AD) plays a detrimental role in synaptic plasticity and cognitive function. The effects of A beta on the early-phase long-term potentiation (E-LTP) have been reported widely. However, whether the late-phase long-term potentiation (L-LTP), which differs from E-LTP mechanistically, is also affected by A beta is still an open question. The present study examined the effects of intracerebraventricular injection of A beta fragments 25-35 and 31-35 on the L-LTP in the CA1 area of rat hippocampus in vivo, and further investigated its possible underlying mechanism. Our results showed that: (1) A beta 25-35 (6.25-25 nmol) did not affect the baseline field excitatory postsynaptic potentials, but dose-dependently suppressed multiple high-frequency stimuli-induced L-LTP; (2) A beta 31-35, a shorter A beta fragment than A beta 25-35, also significantly suppressed L-LTP, with the same suppressive effects as A beta 25-35; (3) pretreatment with PMA (6 nmol/5 mu l), a membrane permeable PKC agonist, effectively prevented A beta 31-35-induced deficits in the early and the late components of L-LTP; (4) co-application of A beta 31-35 and chelerythrine (12 nmol/5 mu l), a PKC antagonist, caused no additive suppression of L-LTP. These results indicate that both A beta 25-35 and A beta 31-35 can impair hippocampal synaptic plasticity in vivo by suppressing the maintenance of L-LTP, and PKC probably mediates the A beta-induced suppression of hippocampal L-LTP. In addition, the similar efficacy of A beta 31-35 and A beta 25-35 in L-LTP suppression supports the hypothesis we suggested previously that the sequence 31-35 in A beta might be the shortest active sequence responsible for the neuronal toxicity induced by full length of A beta molecules. (c) 2008 Elsevier Inc. All rights reserved.
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