Activity-dependent, stress-responsive BDNF signaling and the quest for optimal brain health and resilience throughout the lifespan.
Activity-dependent, stress-responsive BDNF signaling and the quest for optimal brain health and resilience throughout the lifespan.
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DOI：
10.1016/j.neuroscience.2012.10.014
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发表时间：
2013-06-03
期刊：
影响因子：
3.3
通讯作者：
Mattson, M. P.
中科院分区：
文献类型：
--
作者：
Rothman, S. M.;Mattson, M. P.
在神经系统的发育过程中，神经元之间的连接（突触）的形成取决于这些神经元中的电活动，并且由靶细胞产生的神经营养因子在神经网络的这种活动依赖性塑造中起关键作用。在成年哺乳动物中，神经递质和神经营养因子信号通路之间的类似相互作用介导神经网络对环境需求的适应性反应，其中兴奋性神经递质谷氨酸和脑源性神经营养因子（BDNF）是整个中枢神经系统中突触可塑性的特别突出的调节剂。在整个生命周期中，最佳的大脑健康是通过间歇性的挑战来促进的，例如运动，认知刺激和饮食能量限制，这些挑战使神经元受到与活动相关的代谢压力。在分子水平上，对神经元的这种挑战导致参与神经发生、学习和记忆以及神经元存活的蛋白质的产生;实例包括调节线粒体生物发生、蛋白质质量控制以及细胞对氧化、代谢和蛋白毒性应激的抗性的蛋白质。BDNF信号传导介导几种这样的蛋白质的上调，包括蛋白伴侣GRP-78、抗氧化酶、细胞存活蛋白Bcl-2和DNA修复酶APE 1。不充分地暴露于这些挑战，遗传因素可能合谋损害BDNF的产生和/或信号传导，导致大脑易受损伤和神经退行性疾病（包括阿尔茨海默病、帕金森病和亨廷顿病）的影响。此外，BDNF信号传导受糖皮质激素负调控。糖皮质激素通过负性调节棘密度、神经发生和长时程增强来损害脑中的突触可塑性，这些作用可能与糖皮质激素对BDNF的调节有关。研究结果表明，特定脑区的BDNF信号传导介导了运动和能量限制对外周能量代谢和心血管系统的一些有益影响。总的来说，本文中描述的研究结果表明，基于活动依赖性BDNF信号转导，开发最佳大脑健康处方的可能性。
During development of the nervous system, the formation of connections (synapses) between neurons is dependent upon electrical activity in those neurons, and neurotrophic factors produced by target cells play a pivotal role in such activity-dependent sculpting of the neural networks. A similar interplay between neurotransmitter and neurotrophic factor signaling pathways mediates adaptive responses of neural networks to environmental demands in adult mammals, with the excitatory neurotransmitter glutamate and brain-derived neurotrophic factor (BDNF) being particularly prominent regulators of synaptic plasticity throughout the central nervous system. Optimal brain health throughout the lifespan is promoted by intermittent challenges such as exercise, cognitive stimulation and dietary energy restriction, that subject neurons to activity-related metabolic stress. At the molecular level, such challenges to neurons result in the production of proteins involved in neurogenesis, learning and memory and neuronal survival; examples include proteins that regulate mitochondrial biogenesis, protein quality control, and resistance of cells to oxidative, metabolic and proteotoxic stress. BDNF signaling mediates up-regulation of several such proteins including the protein chaperone GRP-78, antioxidant enzymes, the cell survival protein Bcl-2, and the DNA repair enzyme APE1. Insufficient exposure to such challenges, genetic factors may conspire to impair BDNF production and/or signaling resulting in the vulnerability of the brain to injury and neurodegenerative disorders including Alzheimer’s, Parkinson’s and Huntington’s diseases. Further, BDNF signaling is negatively regulated by glucocorticoids. Glucocorticoids impair synaptic plasticity in the brain by negatively regulating spine density, neurogenesis and long-term potentiation, effects that are potentially linked to glucocorticoid regulation of BDNF. Findings suggest that BDNF signaling in specific brain regions mediates some of the beneficial effects of exercise and energy restriction on peripheral energy metabolism and the cardiovascular system. Collectively, the findings described in this article suggest the possibility of developing prescriptions for optimal brain health based on activity-dependent BDNF signaling.
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DOI：
10.1523/jneurosci.5818-10.2011
发表时间：
2011-03-16
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cortese GP;Barrientos RM;Maier SF;Patterson SL
通讯作者：
Patterson SL
影响因子：
4.2
作者：
Adlard, PA;Perreau, VM;Cotman, CW
通讯作者：
Cotman, CW
影响因子：
2.7
作者：
Del Arco, Alberto;Segovia, Gregorio;Mora, Francisco
通讯作者：
Mora, Francisco
DOI：
10.1523/jneurosci.2456-10.2011
发表时间：
2011-04-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Boersma MC;Dresselhaus EC;De Biase LM;Mihalas AB;Bergles DE;Meffert MK
通讯作者：
Meffert MK
影响因子：
11.2
作者：
Arumugam, Thiruma V.;Phillips, Terry M.;Cheng, Aiwu;Morrell, Christopher H.;Mattson, Mark P.;Wan, Ruiqian
通讯作者：
Wan, Ruiqian