AMPA receptors in the therapeutic management of depression
AMPA receptors in the therapeutic management of depression
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DOI：
10.2174/187152707780363258
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发表时间：
2007-04-01
影响因子：
3
通讯作者：
Witkin, J. M.
中科院分区：
文献类型：
--
作者：
Bleakman, D.;Alt, A.;Witkin, J. M.
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）受体在抑郁症和抗抑郁药物中的作用。AMPA受体和其他离子型谷氨酸受体的改变已在抑郁症和抗抑郁药治疗后报道。通过AMPA受体增强信号传导的化合物（AMPA受体增强剂）在动物模型中表现出抗抑郁药样行为效应，并产生与目前可用的抗抑郁药所产生的神经元效应类似的神经元效应，包括神经营养因子诱导和海马祖细胞增殖的增加。此外，已发现抗抑郁药氟西汀以预期增加AMPA受体信号传导的方式改变AMPA受体磷酸化。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，这是一种与抗抑郁治疗作用有关的神经营养因子。结合起来，这些数据表明，AMPA受体可能在调节情绪障碍的关键位置，并且靶向AMPA受体的化合物可能被证明在抑郁症的临床管理中是有用的。
There is an increasing body of evidence implicating a role for (alpha-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 brain-derived 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.