AMPA受体
谷氨酸的
神经科学
吡仑帕奈
海马结构
突触可塑性
谷氨酸受体
沉默突触
长时程增强
长期抑郁
癫痫
生物
受体
生物化学
作者
Laura Bellingacci,Martina Tallarico,Andrea Mancini,Alfredo Megaro,Carmen De,Rita Citraro,Giovambattista De Sarro,Alessandro Tozzi,Massimiliano Di Filippo,Miriam Sciaccaluga,Emilio Russo,Antonio Leo,Cinzia Costa
标识
DOI:10.1016/j.neuropharm.2022.109373
摘要
Pathological accumulation of Aβ oligomers has been linked to neuronal networks hyperexcitability, potentially underpinned by glutamatergic AMPA receptors (AMPARs) dysfunction. We aimed to investigate whether the non-competitive block of AMPARs was able to counteract the alteration of hippocampal epileptic threshold, and of synaptic plasticity linked to Aβ oligomers accumulation, being this glutamate receptor a valuable specific therapeutic target. In this work, we showed that the non-competitive AMPARs antagonist perampanel (PER) which, per se, did not affect physiological synaptic transmission, was able to counteract Aβ-induced hyperexcitability. Moreover, AMPAR antagonism was able to counteract Aβ-induced hippocampal LTP impairment and hippocampal-based cognitive deficits in Aβ oligomers-injected mice, while retaining antiseizure efficacy. Beside this, AMPAR antagonism was also able to reduce the increased expression of proinflammatory cytokines in this mice model, also suggesting the presence of an anti-inflammatory activity. Thus, targeting AMPARs might be a valuable strategy to reduce both hippocampal networks hyperexcitability and synaptic plasticity deficits induced by Aβ oligomers accumulation.
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