Protection against Aβ-mediated rapid disruption of synaptic plasticity and memory by memantine.

Autor: Klyubin I; Department of Pharmacology and Therapeutics, Trinity College, Dublin 2, Ireland., Wang Q, Reed MN, Irving EA, Upton N, Hofmeister J, Cleary JP, Anwyl R, Rowan MJ
Jazyk: angličtina
Zdroj: Neurobiology of aging [Neurobiol Aging] 2011 Apr; Vol. 32 (4), pp. 614-23. Date of Electronic Publication: 2009 May 14.
DOI: 10.1016/j.neurobiolaging.2009.04.005
Abstrakt: Soluble amyloid-β protein (Aβ) may cause cognitive impairment in Alzheimer's disease in the absence of significant neurodegeneration. Here, the ability of the NMDA receptor (NMDAR) antagonist memantine to prevent synthetic Aβ-mediated rapid functional deficits in learned behavior and synaptic plasticity was assessed in the rat. In vitro, pretreatment with a clinically relevant, NMDAR blocking concentration of memantine partially inhibited the induction of long-term potentiation (LTP) in the dentate gyrus and prevented further inhibition caused by exposure to Aβ(1-42). Whereas systemic injection with memantine alone inhibited LTP in the CA1 area in vivo, a subthreshold dose partially abrogated the inhibition of LTP by intracerebroventricular soluble Aβ(1-42). Similarly, systemic treatment with memantine alone impaired performance of an operant learning task and a subthreshold dose prevented the Aβ(1-42)-mediated increase in perseveration errors. The acute protection afforded by memantine, albeit in a narrow dose range, against the rapid disruptive effects of soluble Aβ(1-42) on synaptic plasticity and learned behavior strongly implicate NMDAR-dependent reversible dysfunction of synaptic mechanisms in Aβ-mediated cognitive impairment.
(Copyright © 2009 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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