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Soluble amyloid-β protein (Aβ) plays a central pathogenic role in Alzheimers disease (AD).Memantine, a low-affinity N-methyl-D-aspartate receptor (NMDAR) antagonist, exerts neural protective effects in AD.In this study, we investigated protection of memantine against the neurotoxicity of oligomeric Aβ using electrophysiology methods in vitro and in vivo and behavioral testing.In vitro, incubation of Aβ1-42 oligomers (500 n M) for 40 min prior to HFS strongly prevented LTP.T-his inhibition can be partially reversed by an appropriate dose ofmementine (20 mg/kg, i.p.) treatment for 7 days.However, animals treated with a higher dose (40 mg/kg/day, i.p.) of memantine showed complete abolishment of LTP induction.Likewise, inhibition of LTP by Aβ1-42 is partially restored when we pretreated with memantine (1 μM) for 2 h, but alone treatment use this concentration of memantine for 2 h before HFS would partial inhibited the induction of LTP.In vivo, we found acute injection of soluble Aβ1-42 (40 pmol in 5 μL, i.c.v.) alone 10 min before HFS inhibited LTP, the inhibitory effect of Aβ1-42 was partially prevented when 10 mg/kg memantine was injected 30 min before Aβ1-42.whereas injection of twice this dose (20 mg/kg) alone completely inhibited LTP.In behavioral testing, systemic treatment with memantine (3 mg/kg, i.p) alone impaired performance of operant learning task, but Aβ1-42 failed to strongly increase perseveration errors when the rats also received an injection of the subthreshold dose of memantine (1 mg/kg) if injection of soluble Aβ1-42 (60 pmol in 10 μL) alone before testing expand errors significantly.These findings indicate that memantine restore Aβ oligomers-mediated inhibition of hippocampal LTP in a concentration-related manner both in vitro and in vivo, it also prevented disruptive effect of Aβ1-42 on learned behavior, differences does-related in vitro and in vivo may be due to the different experimental environments and brain regions (the dentate gyrus in vitro and CA 1 area in vivo).Thus, these conclusions provide supplemental evidence for practical application ofmermantine in the treatment of AD.