Oliff H S, Berchtold N C, Isackson P, Cotman C W
Institute for Brain Aging and Dementia, University of California, Irvine, Irvine, CA 92697-4540, USA.
Brain Res Mol Brain Res. 1998 Oct 30;61(1-2):147-53. doi: 10.1016/s0169-328x(98)00222-8.
Previous results from our laboratory indicate that two nights of voluntary wheel running upregulates brain-derived neurotrophic factor (BDNF) mRNA expression in the hippocampus. In order to investigate the time-course of the BDNF response and to examine how physical activity preferentially activates particular transcriptional pathways, the effects of 6 and 12 h of voluntary wheel running on BDNF and exons I-IV mRNA expression were investigated in rats. Hippocampal full-length BDNF mRNA expression was rapidly influenced by physical activity, showing significant increases in expression levels as soon as 6 h of voluntary wheel running. Moreover, there was a strong positive correlation between distance run and BDNF mRNA expression. Exon I mRNA expression was significantly upregulated after 6 h of running and was maintained or enhanced by 12 h of voluntary running. Exon II had a slower time-course and was significantly upregulated after 12 h, selectively in the CA1 hippocampal region. Exon III and Exon IV showed no significant increase in expression level after 6 or 12 h of running in the paradigm studied. It is significant that the rapid neurotrophin response is demonstrated for a physiologically relevant stimulus, as opposed to the extreme conditions of seizure paradigms. Furthermore, exercise-induced upregulation of BDNF may help increase the brain's resistance to damage and neurodegeneration that occurs with aging.
我们实验室之前的研究结果表明，连续两晚自愿进行轮转跑步可上调海马体中脑源性神经营养因子（BDNF）的mRNA表达。为了研究BDNF反应的时间进程，并探究身体活动如何优先激活特定的转录途径，我们对大鼠进行了6小时和12小时自愿轮转跑步，并研究其对BDNF及外显子I-IV mRNA表达的影响。海马体全长BDNF mRNA表达受身体活动的快速影响，在自愿轮转跑步6小时后，表达水平即显著增加。此外，跑步距离与BDNF mRNA表达之间存在很强的正相关性。外显子I mRNA表达在跑步6小时后显著上调，并在12小时自愿跑步后维持或增强。外显子II的时间进程较慢，在12小时后显著上调，且仅在海马体CA1区出现这种情况。在所研究的实验范式中，外显子III和外显子IV在跑步6小时或12小时后，表达水平均未出现显著增加。重要的是，与癫痫发作范式这种极端情况不同，本研究展示了针对生理相关刺激的快速神经营养因子反应。此外，运动诱导的BDNF上调可能有助于增强大脑对衰老过程中出现的损伤和神经退行性变的抵抗力。
