DMXB (GTS-21) ameliorates the cognitive deficits in beta amyloid injected mice through preventing the dysfunction of alpha7 nicotinic receptor
✍ Scribed by Lei Chen; Haofei Wang; Zhuo Zhang; Zhen Li; Danjun He; Masahiro Sokabe; Ling Chen
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 471 KB
- Volume
- 88
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Intracerebroventricular injection of beta-amyloid 25-35 ) in mice leads to cognitive deficits with the dysfunction of a7 nicotinic acetylcholine receptor (a7nAChR) within 1-2 weeks in a dose-dependent manner. The present study focused on the effect of DMXB, a selective a7nAChR agonist, on Ab 25-35 (3 nmol)-impaired spatial memory and a7nAChR function. We found that the treatment with DMXB on days 1-10 after Ab 25-35 injection dose-dependently prevented Ab 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 Ab 25-35induced depression of a7nAChR 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 Ab 25-35 mice, the Ab 25-35 injection significantly attenuated HFS-triggered increase in ERK2 phosphorylation. The treatment with DMXB also rescued the ERK2 phosphorylation triggered by HFS in Ab 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 Ab 25-35 -induced dysfunction of a7nAChR. V