Ivy A S, Rodriguez F G, Garcia C, Chen M J, Russo-Neustadt A A
Department of Biological Sciences, California State University Los Angeles, 5151 State University Drive, Los Angeles, CA 90032, USA.
Pharmacol Biochem Behav. 2003 Apr;75(1):81-8. doi: 10.1016/s0091-3057(03)00044-3.
Antidepressants and physical exercise have been shown to increase the transcription of hippocampal brain-derived neurotrophic factor (BDNF). Much evidence regarding the initial actions of antidepressant medications as well as exercise leads to the hypothesis that noradrenergic (NE) and/or serotonergic (5-HT) activation is a key element in the BDNF transcriptional elevation common to both interventions. Currently, we used short-term beta-adrenergic, 5-HT(1A), or 5-HT(2A/C) receptor blockade to characterize the influence of NE and 5-HT systems on BDNF transcription during physical exercise and antidepressant treatment. In situ hybridization revealed that beta-adrenergic blockade significantly blunted the BDNF mRNA elevations due to exercise, and also inhibited the modest elevations in the CA3 and dentate gyrus following short-term treatment with tranylcypromine. In contrast, 5-HT(2A/C) blockade only minimally altered exercise-induced BDNF mRNA levels, but inhibited up-regulation of BDNF transcription via tranylcypromine. Finally, 5-HT(1A) blockade did not inhibit exercise-induced BDNF mRNA elevations, but significantly enhanced levels above those achieved with exercise alone in the CA4. These results suggest that NE activation via beta-adrenergic receptors may be essential for both exercise and antidepressant-induced BDNF regulation. 5-HT(1A) and 5-HT(2A/C) activation, on the other hand, appear to be most important for antidepressant-induced BDNF regulation, but may also participate significantly in exercise-induced regulation in the CA4.
抗抑郁药和体育锻炼已被证明可增加海马脑源性神经营养因子（BDNF）的转录。大量关于抗抑郁药物以及锻炼的初始作用的证据引出了这样一个假说，即去甲肾上腺素能（NE）和/或5-羟色胺能（5-HT）激活是这两种干预措施共有的BDNF转录升高的关键因素。目前，我们使用短期β-肾上腺素能、5-HT（1A）或5-HT（2A/C）受体阻断来表征NE和5-HT系统在体育锻炼和抗抑郁治疗期间对BDNF转录的影响。原位杂交显示，β-肾上腺素能阻断显著减弱了锻炼引起的BDNF mRNA升高，并且还抑制了在用反苯环丙胺短期治疗后CA3和齿状回中的适度升高。相比之下，5-HT（2A/C）阻断仅轻微改变了锻炼诱导的BDNF mRNA水平，但抑制了反苯环丙胺引起的BDNF转录上调。最后，5-HT（1A）阻断并未抑制锻炼诱导的BDNF mRNA升高，但显著提高了CA4区中高于单独锻炼所达到水平的BDNF水平。这些结果表明，通过β-肾上腺素能受体的NE激活可能对锻炼和抗抑郁药诱导的BDNF调节都至关重要。另一方面，5-HT（1A）和5-HT（2A/C）激活似乎对抗抑郁药诱导的BDNF调节最为重要，但也可能在CA4区的锻炼诱导调节中发挥重要作用。
