Food deprivation induces presynaptic plasticity in the autonomic nervous system.
Food deprivation induces presynaptic plasticity in the autonomic nervous system.
复制标题
食物匮乏会引起自主神经系统的突触前可塑性。
DOI：
10.1073/pnas.1605618113
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发表时间：
2016
影响因子：
11.1
通讯作者：
Anantharam,Arun
中科院分区：
文献类型：
--
作者：
Holz,RonaldW;Anantharam,Arun
交感-肾上腺髓质神经系统是哺乳动物在应激时维持体内平衡的关键组成部分。这个概念最早是由Walter B提出的。坎农人在世纪初提出了“战或逃”反应一词。Hans Selye提出了对各种压力源的统一，系统和非特异性反应的概念，包括交感神经系统的所有部分（1）。然而，最近已经变得明显的是，不同的应激源可以引起不同的交感神经反应。一个例子是低血糖。肾上腺素过少会引起内脏神经（其细胞体位于脊髓中）刺激肾上腺髓质中的嗜铬细胞释放肾上腺素进入循环。肾上腺素的增加有许多代谢作用，会增加血糖。低血糖引起很少或没有激活节后的去甲肾上腺素能交感神经，交感神经系统的另一个主要组成部分（2，3）。在PNAS中，Wang等人研究了交感神经系统对禁食的反应，禁食是一种类似于低血糖的应激（4）。作者发现交感神经反应也是孤立的肾上腺髓质途径。出乎意料的是，他们的研究表明，肾上腺素分泌增加的一个重要组成部分是内脏神经末梢和嗜铬细胞之间胆碱能传递效率的提高。进一步的研究表明，这种突触可塑性的结果从肾上腺髓质内的旁分泌系统。Wang等人(4)首次证明了禁食24小时的小鼠具有正常的血浆葡萄糖、升高的尿肾上腺素和正常的尿去甲肾上腺素。由于肾上腺素的来源是肾上腺髓质，去甲肾上腺素的来源主要是交感神经，这些结果证实了预期的生理学，即饥饿的代谢应激特异性地激活交感神经系统的肾上腺髓质成分。食物剥夺的作用被升高的循环肾上腺素的外周作用抵消，以维持血糖稳态。虽然没有研究，中枢神经系统可能增加了内脏神经的神经冲动频率，支配肾上腺髓质。然而，Wang et al. (4)关注监管的另一个方面，这是以前没有考虑过的。他们研究了食物剥夺时胆碱能内脏神经末梢和嗜铬细胞之间突触的强度（图1）。首先，他们用电刺激突触前神经末梢。作者发现，食物剥夺后兴奋性突触后电流（EPSC）显著增大。较大的EPSC可能反映了突触前胞吐的增加，嗜铬细胞对乙酰胆碱的敏感性增加，或两者兼而有之。第二种方法表明，增加的突触传递的一个组成部分是突触前。Wang等人(4)使用成对脉冲比率技术来探测突触前机制。突触前神经
The sympathetic-adrenal medullary nervous system is a key component of the response of mammals to maintain homeostasis during stress. This notion was first articulated by Walter B. Cannon in the early 20th century, who introduced the term “fight or flight” response. Hans Selye promoted the notion of a unified, systemic and nonspecific response to a variety of stressors that includes all parts of the sympathetic nervous system (1). However, more recently it has become evident that different stressors can elicit different sympathetic responses. One example is hypoglycemia. Hypoglycemia causes the splanchnic nerve, whose cell bodies are in the spinal cord, to stimulate chromaffin cells in the adrenal medulla to release epinephrine into the circulation. The increased epinephrine has numerous metabolic effects that increase blood glucose.Hypoglycemia causes little or no activation of postganglionic, noradrenergic sympathetic nerves, another major component of the sympathetic nervous system (2, 3). In PNAS Wang et al. investigate the response of the sympathetic nervous system to fasting, a stress similar to hypoglycemia (4). The authors find that the sympathetic response is also isolated to the adrenal medullary pathway. Unexpectedly, their study suggests that an important component of the increased secretion of epinephrine results from increased efficiency of cholinergic transmission between the splanchnic nerve terminal and the chromaffin cell. Further investigation suggests that this synaptic plasticity results from a paracrine system within the adrenal medulla. Wang et al.(4) first demonstrate that mice that are food-deprived for 24 h had normal plasma glucose, elevated urinary epinephrine, and normal urinary norepinephrine. Because the source of epinephrine is the adrenal medulla and the source of norepinephrine is mainly sympathetic nerves, these results confirm the expected physiology that the metabolic stress of starvation specifically activates the adrenal medullary component of the sympathetic nervous system. The effects of food deprivation are countered by the peripheral effects of elevated circulating epinephrine to maintain plasma glucose homeostasis. Although not investigated, the central nervous system may have increased the frequency of nerve impulses in the splanchnic nerve, innervating the adrenal medulla. However, Wang et al.(4) focus on another aspect of regulation that had not been previously considered. They investigated the strength of the synapses between cholinergic splanchnic nerve terminals and chromaffin cells upon food deprivation (Fig. 1). First, they electrically stimulated the presynaptic nerve terminals. The authors found that the excitatory postsynaptic currents (EPSCs) were significantly larger following food deprivation. The larger EPSCs could reflect an increase in presynaptic exocytosis, increased sensitivity of chromaffin cells to acetylcholine, or both. The second approach indicated that a component of the increased synaptic transmission is presynaptic. Wang et al.(4) used the paired-pulse ratio technique to probe presynaptic mechanisms. Presynaptic nerves