Pae Chi-Un, Marks David M, Han Changsu, Patkar Ashwin A, Steffens David
Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, South Korea.
Int J Neurosci. 2008 Nov;118(11):1515-22. doi: 10.1080/00207450802174589.
Although several classes of antidepressants are used to treat major depression, there is an unmet need in real clinical practice because not all patients treated with an antidepressant fully recover from their functional impairment. Hence, the development of new antidepressants based on a novel therapeutic mechanism may help in the development of more effective and ideal antidepressive agents. There is emerging evidence suggesting that the etiopathogenesis of depression involves transmitters other than the major neurotransmitters such as serotonin, norepinephrine, and dopamine. Therefore, it has consistently been suggested that an alteration in neuroprotection and synaptic plasticity is associated with the pathogenesis and therapeutic mechanism of depression. Neurotropin-3 (NT3) is an interesting protein that regulates neuronal survival, synaptic plasticity, and neurotransmission. It is widely expressed in the hippocampus and facilitates hippocampal plasticity by regulating neurogenesis. It has been also reported that an infusion of NT3 increases the level of brain-derived neurotrophic factor (BDNF) mRNA expression in the cerebral cortex and produces BDNF-like effects that induce cortical tyrosine kinase B phosphorylation. BDNF has been consistently implicated in the pathogenesis of depression and the therapeutic mechanism of antidepressants. It has also been implicated in the treatment effect of mood stabilizers such as lithium. NT3 has demonstrated its possible antidepressant effect in a learned helpless animal model. Animal studies have shown that it also modulates the neurotransmitters, serotonin and noradrenaline, which are essential in the development and treatment of depression. Therefore, further studies on the therapeutic implications of NT3 for depression are warranted and are expected for the development of newer, effective antidepressants.
尽管几类抗抑郁药被用于治疗重度抑郁症，但在实际临床实践中仍存在未满足的需求，因为并非所有接受抗抑郁药治疗的患者都能从功能障碍中完全康复。因此，基于新型治疗机制开发新的抗抑郁药可能有助于开发更有效、更理想的抗抑郁剂。越来越多的证据表明，抑郁症的病因涉及血清素、去甲肾上腺素和多巴胺等主要神经递质以外的递质。因此，一直有人认为神经保护和突触可塑性的改变与抑郁症的发病机制和治疗机制有关。神经营养素-3（NT3）是一种有趣的蛋白质，它调节神经元存活、突触可塑性和神经传递。它在海马体中广泛表达，并通过调节神经发生促进海马体可塑性。也有报道称，注入NT3可增加大脑皮质中脑源性神经营养因子（BDNF）mRNA的表达水平，并产生类似BDNF的作用，诱导皮质酪氨酸激酶B磷酸化。BDNF一直与抑郁症的发病机制和抗抑郁药的治疗机制有关。它也与锂等心境稳定剂的治疗效果有关。NT3已在习得性无助动物模型中显示出其可能的抗抑郁作用。动物研究表明，它还调节血清素和去甲肾上腺素等神经递质，这些神经递质在抑郁症的发生和治疗中至关重要。因此，有必要对NT3对抑郁症的治疗意义进行进一步研究，有望开发出更新、更有效的抗抑郁药。
