科研之友
微信
新浪微博
Facebook
分享链接
摘要
Aggregated amyloid ss-protein (A ss) is pathognomonic of Alzheimer's disease and certain assemblies of A ss are synaptotoxic. Excess glutamate or diminished glutathione reserve are both implicated in mediating or modulating A ss-induced disruption of synaptic plasticity. The system antiporter promotes Na+-independent exchange of cystine with glutamate thereby providing a major source of extracellular glutamate and intracellular glutathione concentrations. Here we probed the ability of two drugs with opposite effects on system , the inhibitor sulfasalazine and facilitator N-acetylcysteine, to modulate the ability of A ss 1-42 to inhibit long-term potentiation (LTP) in the CA1 area of the anaesthetized rat. Whereas acute systemic treatment with sulfasalazine lowered the threshold for A ss to interfere with synaptic plasticity, N-acetylcysteine prevented the inhibition of LTP by A ss alone or in combination with sulfasalazine. Moreover acute N-acetylcysteine also prevented the inhibition of LTP by TNF, a putative mediator of A ss actions, and repeated systemic N-acetylcysteine treatment for 7 days reversed the delayed deleterious effect of A ss on LTP. Since both of these drugs are widely used clinically, further evaluation of their potential beneficial and deleterious actions in early Alzheimer's disease seems warranted.
- 出版日期2016-12
- 单位新乡医学院
