Fasting induces a form of autonomic synaptic plasticity that prevents hypoglycemia.
Fasting induces a form of autonomic synaptic plasticity that prevents hypoglycemia.
复制标题
禁食会诱导一种自主神经突触可塑性，从而预防低血糖。
DOI：
10.1073/pnas.1517275113
复制
发表时间：
2016
影响因子：
11.1
通讯作者：
Whim,MatthewD
中科院分区：
文献类型：
--
作者：
Wang,Manqi;Wang,Qian;Whim,MatthewD
在禁食期间，激活反调节反应（CRR）可预防低血糖。一个主要的效应臂是自主神经系统，它控制肾上腺嗜铬细胞释放肾上腺素，从而控制肝葡萄糖的产生。然而，自主神经功能的调节是否决定了CRR的相对强度，从而决定了耐受食物剥夺和维持健康的能力，目前尚不清楚。在这里，我们表明，禁食导致改变传输在节前→嗜铬细胞突触。主要效应是突触前突触强度的持久增加。使用遗传和药理学方法，我们表明这种可塑性需要神经肽Y，肾上腺共递质和肾上腺Y5受体的激活。神经肽Y的缺失阻止了禁食诱导的肾上腺素释放增加，并导致体内低血糖。这些发现将交感神经系统内的可塑性与生理输出联系起来，并表明下行通路中最后一个突触的强度在维持神经功能正常方面起着决定性作用。
During fasting, activation of the counter-regulatory response (CRR) prevents hypoglycemia. A major effector arm is the autonomic nervous system that controls epinephrine release from adrenal chromaffin cells and, consequently, hepatic glucose production. However, whether modulation of autonomic function determines the relative strength of the CRR, and thus the ability to withstand food deprivation and maintain euglycemia, is not known. Here we show that fasting leads to altered transmission at the preganglionic → chromaffin cell synapse. The dominant effect is a presynaptic, long-lasting increase in synaptic strength. Using genetic and pharmacological approaches we show this plasticity requires neuropeptide Y, an adrenal cotransmitter and the activation of adrenal Y5 receptors. Loss of neuropeptide Y prevents a fasting-induced increase in epinephrine release and results in hypoglycemia in vivo. These findings connect plasticity within the sympathetic nervous system to a physiological output and indicate the strength of the final synapse in this descending pathway plays a decisive role in maintaining euglycemia.