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. 2010 Sep;161(1):127–139. doi: 10.1111/j.1476-5381.2010.00894.x

Figure 2.

Figure 2

Neuroprotective effect of donepezil (Dpz) against glutamate (Glu)-induced caspase-3 activation and excitotoxicity was mediated via α7 nAChR and a Src family tyrosine kinase. (A) Dpz-induced neuroprotection (10 µM) against glutamate (Glu) excitotoxicity was concentration-dependent. Pre-treatment with Dpz for 48 h followed by 24-h Glu (30 µM) with Dpz incubation. n = 32. *P < 0.05 compared with control (vehicle alone), †P < 0.05 compared with Glu alone. Statistically significant differences between groups were determined by Kruskal–Wallis analysis of variance (anova) followed by Dunn's post-test. (B) Dpz (10 µM)-induced neuroprotection against Glu (30 µM, 24 h) excitotoxicity was mediated via α7 nAChR. Simultaneous administration of MLA (1 µM), α7 nAChR antagonist, attenuated Dpz-induced neuroprotection. n = 32. *P < 0.05 compared with control (vehicle alone), †P < 0.05 compared with Glu alone, #P < 0.05 compared with Dpz + Glu. Statistically significant differences between groups were determined by Kruskal–Wallis anova followed by Dunn's post-test. (C) Dpz-induced neuroprotection (10 µM) against Glu (30 µM, 24 h) excitotoxicity was mediated via a Src family tyrosine kinase. PP2 (5 µM), a Src family tyrosine kinase inhibitor, reduced Dpz-induced neuroprotection. n = 32. *P < 0.05 compared with control (vehicle alone), †P < 0.05 compared with Glu alone, #P < 0.05 compared with Dpz + Glu. Statistically significant differences between groups were determined by Kruskal–Wallis anova followed by Dunn's post-test. (D) Glu-induced caspase-3-like activity (30 µM) was reduced by Dpz. Glu increased caspase-3-like activity and reached its peak at 3 h treatment. Pre-treatment of Dpz (10 µM, 48 h) attenuated the Glu-induced caspase-3 like activity. n = 6. *P < 0.05 compared with Glu alone. Statistically significant differences between groups were determined by Kruskal-Wallis anova followed by Dunn's post-test. (E) Cleaved caspase-3, an activated form of caspase-3, was also increased by Glu and inhibited by Dpz pre-treatment (10 µM, 48 h).