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DMXB (GTS‐21) ameliorates the cognitive deficits in beta amyloid 25–35 − injected mice through preventing the dysfunction of alpha7 nicotinic receptor
Author(s) -
Chen Lei,
Wang Haofei,
Zhang Zhuo,
Li Zhen,
He Danjun,
Sokabe Masahiro,
Chen Ling
Publication year - 2010
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22345
Subject(s) - long term potentiation , hippocampus , morris water navigation task , agonist , acetylcholine , hippocampal formation , pharmacology , nicotinic agonist , stimulation , neuroscience , endocrinology , medicine , phosphorylation , amyloid beta , chemistry , receptor , psychology , biochemistry , disease
Intracerebroventricular injection of beta‐amyloid 25–35 (Aβ 25–35 ) in mice leads to cognitive deficits with the dysfunction of α7 nicotinic acetylcholine receptor (α7nAChR) within 1–2 weeks in a dose‐dependent manner. The present study focused on the effect of DMXB, a selective α7nAChR agonist, on Aβ 25–35 (3 nmol)‐impaired spatial memory and α7nAChR function. We found that the treatment with DMXB on days 1–10 after Aβ 25–35 injection dose‐dependently prevented Aβ 25–35 ‐induced impairment of acquisition performance and probe trail test in Morris water maze. Importantly, the treatment with DMXB (1 mg/kg) perfectly prevented Aβ 25–35 ‐induced depression of α7nAChR response, which was associated with improving the probability of presynaptic glutamate release and the induction of high‐frequency stimulation (HFS)‐dependent long‐term potentiation (LTP) in hippocampal Schaffer collaterale‐CA1 synapse. Furthermore, although either the basal level of extracellular signal‐regulated kinase 2 (ERK2) or its phosphorylation in the hippocampus had no difference between control and Aβ 25–35 mice, the Aβ 25–35 injection significantly attenuated HFS‐triggered increase in ERK2 phosphorylation. The treatment with DMXB also rescued the ERK2 phosphorylation triggered by HFS in Aβ 25–35 mice that is required for LTP induction. This study firstly provides in vivo evidence that the anti‐amnesic effect of DMXB is likely due to preventing the Aβ 25–35 ‐induced dysfunction of α7nAChR. © 2010 Wiley‐Liss, Inc.