Drzyzga Łukasz R, Marcinowska Agnieszka, Obuchowicz Ewa
Medical University of Silesia, Department of Pharmacology, Medyków 18, 40-752 Katowice, Poland.
Brain Res Bull. 2009 Jun 30;79(5):248-57. doi: 10.1016/j.brainresbull.2009.03.009. Epub 2009 Apr 5.
Recent studies have strengthened the role of the abnormalities in neurotrophic pathways in the pathophysiology of depression. It has been shown that the depletion of growth factors, particularly brain-derived neurotrophic factor, may result in depression-like behavior in animals and may induce cellular changes that are reminiscent of those observed in depressed patients. Some authors even suggested that increased neuronal cell loss may contribute to the pathogenesis of depression. Hence, appreciable interest has been focused on the trophic and antiapoptotic effects of antidepressant drugs. In this paper, we put emphasis on the contribution of hippocampal atrophy, increased cell death and alterations in trophic factors to the pathogenesis of depression and their relationship to the potential of antidepressants to reverse these changes by modulating trophic factor cascades and preventing apoptosis. First, evidences for increased hippocampal atrophy and cell death in depression are discussed, followed by a review of selected studies of special interest that concern antiapoptotic action of antidepressant drugs. Next, depression-related neurotrophic abnormalities and their reversal by antidepressants are depicted. Finally, relationships among neurotrophins, antiapoptotic proteins and antioxidant enzymes in the pathology and treatment of depression are pointed out.
最近的研究强化了神经营养通路异常在抑郁症病理生理学中的作用。研究表明，生长因子尤其是脑源性神经营养因子的耗竭，可能导致动物出现类似抑郁的行为，并可能引发一些细胞变化，这些变化让人联想到在抑郁症患者身上观察到的变化。一些作者甚至认为，神经元细胞丢失增加可能是抑郁症发病机制的一个因素。因此，抗抑郁药物的营养和抗凋亡作用受到了相当大的关注。在本文中，我们重点阐述海马萎缩、细胞死亡增加以及营养因子改变对抑郁症发病机制的影响，以及它们与抗抑郁药物通过调节营养因子级联反应和预防细胞凋亡来逆转这些变化的潜力之间的关系。首先，讨论抑郁症中海马萎缩和细胞死亡增加的证据，随后回顾一些关于抗抑郁药物抗凋亡作用的特别有趣的研究。接下来，描述与抑郁症相关的神经营养异常以及抗抑郁药物对其的逆转作用。最后，指出神经营养因子、抗凋亡蛋白和抗氧化酶在抑郁症病理和治疗中的关系。
