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AMPA Receptors in the Therapeutic Management of Depression

机译:AMPA受体在抑郁症的治疗管理中

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摘要

There is an increasing body of evidence implicating a role for α-amino-3-hydroxy-5-methyl-4 isoxazoleproprionic acid (AMPA) receptors in major depression and in the actions of antidepressant drugs. Alterations in AMPA receptors and other ionotropic glutamate receptors have been reported in depression, and following antidepressant treatment. Compounds which augment signaling through AMPA receptors (AMPA receptor potentiators) exhibit antidepressant-like behavioral effects in animal models, and produce neuronal effects similar to those produced by currently available antidepressants, including neurotrophin induction and increases in hippocampal progenitor cell proliferation. Additionally, the antidepressant fluoxetine has been found to alter AMPA receptor phosphorylation in a manner that is expected to increase AMPA receptor signaling. Data from mutant mice suggest that AMPA receptors may regulate the expression of brainderived neurotrophic factor, a neurotrophin which has been implicated in the actions of antidepressant therapies. Combined, these data suggest that AMPA receptors may be in a key position to regulate mood disorders, and that compounds which target AMPA receptors may prove useful in the clinical management of depression.
机译:越来越多的证据表明α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体在严重抑郁症和抗抑郁药的作用中起作用。据报道,在抑郁症和抗抑郁药治疗后,AMPA受体和其他离子型谷氨酸受体发生了变化。通过AMPA受体(AMPA受体增强剂)增强信号传导的化合物在动物模型中表现出抗抑郁样的行为作用,并产生类似于当前可用抗抑郁药产生的神经元作用,包括神经营养因子诱导和海马祖细胞增殖增加。另外,已经发现抗抑郁剂氟西汀以预期增加AMPA受体信号传导的方式改变AMPA受体的磷酸化。来自突变小鼠的数据表明,AMPA受体可能调节脑源性神经营养因子的表达,这是一种神经营养蛋白,与抗抑郁药的作用有关。综合起来,这些数据表明,AMPA受体可能在调节情绪障碍中处于关键位置,而且靶向AMPA受体的化合物可能被证明可用于抑郁症的临床治疗。

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