Russo-Neustadt A A, Beard R C, Huang Y M, Cotman C W
Institute for Brain Aging and Dementia, University of California, Irvine, California, USA.
Neuroscience. 2000;101(2):305-12. doi: 10.1016/s0306-4522(00)00349-3.
Brain-derived neurotrophic factor, the most abundant of the neurotrophins in the brain, enhances the growth and maintenance of several neuronal systems, serves as a neurotransmitter modulator, and participates in use-dependent plasticity mechanisms such as long-term potentiation and learning. In recent years, evidence has been gathering that brain-derived neurotrophic factor may have an important role in the neuropathology and treatment of depression. It has recently been reported that chronic (at least two weeks) antidepressant treatment leads to an up-regulation of brain-derived neurotrophic factor messenger RNA levels in the hippocampus, an important brain area for behavioral regulation, as well as learning and memory. Our laboratory has previously shown that general physical exercise very rapidly increases brain-derived neurotrophic factor messenger RNA in this brain area. In this report, we have tested the hypothesis that the combination of these two interventions, general physical activity and antidepressant treatment, leads to increased levels of specific promoter-derived transcripts of brain-derived neurotrophic factor messenger RNA in a manner that appears to be both additive and accelerated. Our results suggest that these two very different interventions may possibly converge at the cellular level. The induction of brain-derived neurotrophic factor expression by activity/pharmacological treatment combinations could represent an important intervention for further study, to potentially improve depression treatment and management.
脑源性神经营养因子是大脑中含量最为丰富的神经营养因子，可促进多种神经元系统的生长和维持，作为神经递质调节剂，并参与诸如长时程增强和学习等依赖于使用的可塑性机制。近年来，越来越多的证据表明，脑源性神经营养因子可能在抑郁症的神经病理学及治疗中发挥重要作用。最近有报道称，慢性（至少两周）抗抑郁治疗会导致海马体（行为调节以及学习和记忆的一个重要脑区）中脑源性神经营养因子信使核糖核酸水平上调。我们实验室此前已表明，一般体育锻炼能非常迅速地增加该脑区的脑源性神经营养因子信使核糖核酸。在本报告中，我们检验了这样一个假设：一般体育活动和抗抑郁治疗这两种干预措施相结合，会以一种似乎具有累加性和加速性的方式导致脑源性神经营养因子信使核糖核酸特定启动子衍生转录本水平升高。我们的结果表明，这两种截然不同的干预措施可能在细胞水平上产生协同作用。通过活动/药物治疗组合诱导脑源性神经营养因子表达可能代表着一种重要的干预措施以供进一步研究，从而有可能改善抑郁症的治疗和管理。
