Dietary energy intake modifies brainstem autonomic dysfunction caused by mutant α-synuclein.
Dietary energy intake modifies brainstem autonomic dysfunction caused by mutant α-synuclein.
复制标题
饮食能量摄入可修饰由突变α-突触核蛋白引起的脑干自主神经功能障碍。
DOI：
10.1016/j.neurobiolaging.2012.07.008
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发表时间：
2013-03
影响因子：
4.2
通讯作者：
Mattson MP
中科院分区：
文献类型：
--
作者：
Griffioen KJ;Rothman SM;Ladenheim B;Wan R;Vranis N;Hutchison E;Okun E;Cadet JL;Mattson MP
帕金森氏病(PD)患者通常表现出自主神经系统(ANS)对心率的调节受损，在许多情况下可能先于运动症状。尸检结果表明，帕金森病患者的脑干病理，包括α-突触核蛋白的积聚，先于黑质多巴胺能神经元的损害。然而，导致脑干自主神经早期功能障碍的分子和细胞机制尚不清楚。在此，我们报道了表达突变形式的α-突触核蛋白导致家族性帕金森病的小鼠表现出以静息心率加快和心血管应激反应受损为特征的心脏自主神经异常控制，并与副交感神经活性降低和α-突触核蛋白在脑干中的积累有关。这些ANS异常发生在疾病过程的早期。高能量饮食加剧了α-突触核蛋白对心率控制的不利影响，而间歇性能量限制则缓解了这种不良影响。我们的发现建立了帕金森病患者早期脑干控制心血管系统失调的小鼠模型，并进一步表明限制能量可能会减轻ANS功能障碍，特别是在超重人群中。
Parkinson’s disease (PD) patients often exhibit impaired regulation of heart rate by the autonomic nervous system (ANS) that may precede motor symptoms in many cases. Results of autopsy studies suggest that brainstem pathology, including the accumulation of α-synuclein, precedes damage to dopaminergic neurons in the substantia nigra in PD. However, the molecular and cellular mechanisms responsible for the early dysfunction of brainstem autonomic neurons are unknown. Here we report that mice expressing a mutant form of α-synuclein that causes familial PD exhibit aberrant autonomic control of the heart characterized by elevated resting heart rate and an impaired cardiovascular stress response, associated with reduced parasympathetic activity and accumulation of α-synuclein in the brainstem. These ANS abnormalities occur early in the disease process. Adverse effects of α-synuclein on the control of heart rate are exacerbated by a high energy diet and ameliorated by intermittent energy restriction. Our findings establish a mouse model of early dysregulation of brainstem control of the cardiovascular system in PD, and further suggest the potential for energy restriction to attenuate ANS dysfunction, particularly in overweight individuals.
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影响因子：
6.1
作者：
Hallett PJ;McLean JR;Kartunen A;Langston JW;Isacson O
通讯作者：
Isacson O
影响因子：
4.8
作者：
Martin, Bronwen;Pearson, Michele;Mattson, Mark P.
通讯作者：
Mattson, Mark P.
影响因子：
11.2
作者：
HALLIDAY, GM;LI, YW;GEFFEN, LB
通讯作者：
GEFFEN, LB
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
影响因子：
4.2
作者：
Griffioen, Kathleen J.;Wan, Ruiqian;Mattson, Mark P.
通讯作者：
Mattson, Mark P.