The influence of specific noradrenergic and serotonergic lesions on the expression of hippocampal brain-derived neurotrophic factor transcripts following voluntary physical activity
The influence of specific noradrenergic and serotonergic lesions on the expression of hippocampal brain-derived neurotrophic factor transcripts following voluntary physical activity
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DOI：
10.1016/s0306-4522(03)00192-1
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Russo-Neustadt, A
中科院分区：
文献类型：
--
作者：
Garcia, C;Chen, MJ;Russo-Neustadt, A
先前的研究表明，海马脑源性神经营养因子（BDNF）mRNA水平显着增加大鼠允许自由进入运动轮和/或管理抗抑郁药物。BDNF的增强可能对抗抑郁干预的临床效果至关重要。由于去甲肾上腺素能和/或去甲肾上腺素能系统的功能增加被认为是抗抑郁药物的重要初始机制，我们试图检验去甲肾上腺素能或去甲肾上腺素能功能对于运动引起的BDNF转录增加是必不可少的这一假设。此外，BDNF的个别转录变体进行了检查，因为存在的证据表明，它们受到离散干预的差异调节，并在海马体的不同亚区中表达。在开始自愿轮跑活动之前，对大鼠给予神经递质系统特异性神经毒素对氯苯丙胺（肾上腺素能）和N-（2-氯乙基）-N-乙基-2-溴苄胺（去甲肾上腺素能）。原位杂交实验显示，在去甲肾上腺素能损伤大鼠的大脑中动脉中，没有运动诱导的全长BDNF mRNA升高。此外，显著升高的外显子I转录在齿状回被删除与此去甲肾上腺素能病变。与此相反，其他转录变体（外显子II和III）升高，在几个海马区作为这种病变的结果。在降钙素损伤大鼠中，全长BDNF、外显子I和外显子11 mRNA水平的显著增加持续不变（除了在山茱萸亚区4，CA 4中的外显子IV）。总之，这些结果表明，一个完整的去甲肾上腺素能系统可能是至关重要的观察到的能力，运动，以提高全长和外显子I海马BDNF mRNA的表达。此外，这些结果表明，启动子连接到外显子I可能提供了一个主要的调节点BDNF mRNA的表达在齿状回。其他外显子的升高，如11和III，可能需要激活单独的神经传递系统和细胞内途径。(C)2003年IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
Previous studies have shown that hippocampal brain-derived neurotrophic factor (BDNF) mRNA levels are significantly increased in rats allowed free access to exercise wheels and/or administered antidepressant medications. Enhancement of BDNF may be crucial for the clinical effect of antidepressant interventions. Since increased function of the noradrenergic and/or serotonergic systems is thought to be an important initial mechanism of antidepressant medications, we sought to test the hypothesis that noradrenergic or serotonergic function is essential for the increased BDNF transcription occurring with exercise. In addition, individual transcript variants of BDNF were examined, as evidence exists they are differentially regulated by discrete interventions, and are expressed in distinct sub-regions of the hippocampus. The neurotransmitter system-specific neurotoxins p-chloroamphetamine (serotonergic) and N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (noradrenergic) were administered to rats prior to commencing voluntary wheel-running activity. In situ hybridization experiments revealed an absence of exercise-induced full-length BDNF mRNA elevations in the hippocampi of noradrenergic-lesioned rats. In addition, the striking elevation of the exon I transcript in the dentate gyrus was removed with this noradrenergic lesion. In contrast, other transcript variants (exons II and III) were elevated in several hippocampal regions as a result of this lesion. In serotonin-lesioned rats, the significant increases in full-length BDNF, exon I and exon 11 mRNA levels were sustained without alteration (with the exception of exon IV in the cornus ammonis subregion 4, CA4). Overall, these results indicate that an intact noradrenergic system may be crucial for the observed ability of exercise to enhance full-length and exon I hippocampal BDNF mRNA expression. In addition, these results suggest that the promoter linked to exon I may provide a major regulatory point for BDNF mRNA expression in the dentate gyrus. Elevations of other exons, such as 11 and III, may require the activation of separate neurotransmiltter systems and intracellular pathways. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.