Beta-amyloid inhibition of long-term potentiation is mediated via tumor necrosis factor.
Beta-amyloid inhibition of long-term potentiation is mediated via tumor necrosis factor.
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发表时间：
2005
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通讯作者：
Qinwen Wang;Jinqun Wu;M. Rowan;R. Anwyl
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作者：
Qinwen Wang;Jinqun Wu;M. Rowan;R. Anwyl
最近的一些研究表明，β-淀粉样蛋白（Abeta）抑制海马长时程增强（LTP）的诱导。然而，很少有人知道这种抑制LTP的机制。在目前的研究中，我们提出的证据表明，细胞因子肿瘤坏死因子（TNF）α在抑制LTP的Abeta的关键作用。在TNF受体1型（TNF-R1）缺失的突变小鼠中，不存在A β对LTP的抑制作用，TNF α抑制剂英夫利西单抗和TNF肽拮抗剂以及TNF α产生抑制剂沙利度胺可阻止A β对LTP的抑制作用。此外，外源性TNF α抑制LTP诱导，这是一种通过TNF-R1介导的作用，因为这种抑制在TNF-R1缺失的突变小鼠中不存在。TNF α对LTP的抑制作用涉及I组代谢型谷氨酸受体和p38 MAP激酶的激活，与A β介导的LTP诱导抑制作用相同。
A number of recent studies have shown that beta-amyloid (Abeta) inhibits the induction of long-term potentiation (LTP) in the hippocampus. However, little is known about the mechanisms underlying such inhibition of LTP. In the present study, we present evidence that the cytokine tumor necrosis factor (TNF) alpha has a key role in the Abeta inhibition of LTP. The suppression of LTP by Abeta was absent in mutant mice null for TNF receptor type 1 (TNF-R1) and was prevented by the inhibitors of TNFalpha, infliximab and TNF peptide antagonist, and by the inhibitor of TNFalpha production, thalidomide. In addition, exogenous TNFalpha inhibited LTP induction, an action mediated via TNF-R1 as such inhibition was absent in mutant mice null for TNF-R1. The inhibition of LTP by TNFalpha involved activation of group I metabotropic glutamate receptor and p38 MAP kinase, identical to that for the Abeta-mediated inhibition of LTP induction.