Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease.
Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease.
复制标题
能量代谢和神经元电路功能障碍的破坏性障碍和阿尔茨海默氏病。
DOI：
10.1016/s1474-4422(10)70277-5
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发表时间：
2011-02
期刊：
影响因子：
48
通讯作者：
Mattson, M. P.
中科院分区：
文献类型：
--
作者：
Kapogiannis, D.;Mattson, M. P.
流行病学、神经病理学和功能性神经影像学证据表明，在认知障碍的发病机制中，大脑代谢和能量学的整体和区域紊乱。神经细胞微电路被兴奋性和抑制性突触活动以及神经营养因子自适应地修改。衰老和阿尔茨海默病（Alzheimer's disease，AD）引起细胞能量代谢、兴奋/抑制水平和神经营养因子释放的紊乱，这些紊乱压倒了代偿机制，导致神经元微回路和脑网络功能障碍。长期的正能量平衡损害神经元适应性地响应氧化和代谢应激的能力。动物实验研究表明，与慢性正能量平衡相关的紊乱，如糖尿病，为加速认知老化和AD奠定了基础。针对能量代谢和适应性应激反应（如神经营养因子信号传导）的缓解认知功能障碍的治疗干预措施已在动物模型和人类初步研究中显示出疗效。
Epidemiological, neuropathological and functional neuroimaging evidence implicates global and regional derangements in brain metabolism and energetics in the pathogenesis of cognitive impairment. Nerve cell microcircuits are modified adaptively by excitatory and inhibitory synaptic activity and neurotrophic factors. Aging and Alzheimer’s disease (AD) cause perturbations in cellular energy metabolism, level of excitation/inhibition and neurotrophic factor release that overwhelm compensatory mechanisms and result in neuronal microcircuit and brain network dysfunction. A prolonged positive energy balance impairs the ability of neurons to respond adaptively to oxidative and metabolic stress. Experimental studies in animals demonstrate how derangements related to chronic positive energy balance, such as diabetes, set the stage for accelerated cognitive aging and AD. Therapeutic interventions to allay cognitive dysfunction that target energy metabolism and adaptive stress responses (such as neurotrophin signaling) have shown efficacy in animal models and preliminary studies in humans.