The extracellular signal-regulated kinase pathway: an emerging promising target for mood stabilizers
The extracellular signal-regulated kinase pathway: an emerging promising target for mood stabilizers
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DOI：
10.1097/01.yco.0000218604.63463.cd
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发表时间：
2006-05-01
影响因子：
6.9
通讯作者：
Manji, HK
中科院分区：
文献类型：
--
作者：
Chen, G;Manji, HK
越来越多的人认识到，虽然不是典型的神经退行性疾病，但严重的情绪障碍与结构可塑性和细胞弹性的区域损伤有关。最近令人兴奋的数据表明，突触可塑性可能与情绪稳定剂和抗抑郁药的作用机制有关。值得注意的是，细胞外信号调节激酶途径是大脑中一个关键的“可塑性途径”。本文综述了细胞外信号调节激酶通路在调节双相情感障碍某些症状中的作用以及作为情绪稳定剂的治疗相关靶点的神经生物学、药理学和行为学数据。细胞外信号调节激酶通路介导神经营养作用和突触可塑性。锂和丙戊酸盐可以激活培养细胞、前额皮质和海马的细胞外信号调节激酶通路。此外，锂或丙戊酸盐治疗可促进神经发生、神经突生长和细胞存活。细胞外信号调节激酶途径也是抗精神病药物的靶点。中枢神经系统细胞外信号调节激酶通路的调节诱导动物行为改变，使人联想到躁狂症状；这些复杂的行为可能取决于细胞外信号调节激酶对离散脑区的作用和其他相互作用分子的存在。细胞外信号调节激酶途径可能代表了双相情感障碍改进治疗方法发展的新靶点。
Purpose of review There exists a growing appreciation that, though not classical neurodegenerative disorders, severe mood disorders are associated with regional impairments of structural plasticity and cellular resilience. Exciting recent data suggest that synaptic plasticity probably is involved in mechanisms of actions of mood stabilizers and antidepressants. Notably, the extracellular signal-regulated kinase pathway is a critical 'plasticity pathway' in the brain. The present review summarizes neurobiological, pharmacological, and behavioral data on the role of the extracellular signal-regulated kinase pathway in regulating some of the symptoms of bipolar disorder and as a therapeutically relevant target for mood stabilizers.Recent findings The extracellular signal-regulated kinase pathway is known to mediate neurotrophic actions and synaptic plasticity. Treatment with lithium and valproate activates the extracellular signal-regulated kinase pathway in cultured cells and in prefrontal cortex and hippocampus. In addition, lithium or valproate treatment promotes neurogenesis, neurite growth, and cell survival. The extracellular signal-regulated kinase pathway is also targeted by antipsychotics. Modulation of the central nervous system extracellular signal-regulated kinase pathway induces animal behavioral alterations reminiscent of manic symptoms; these complex behaviors probably depend on the effects of extracellular signal-regulated kinase on discrete brain regions and the presence of other interacting molecules.Summary The extracellular signal-regulated kinase pathway may represent a novel target for the development of improved therapeutics for bipolar disorder.