Negative Energy Balance Blocks Neural and Behavioral Responses to Acute Stress by "Silencing" Central Glucagon-Like Peptide 1 Signaling in Rats
Negative Energy Balance Blocks Neural and Behavioral Responses to Acute Stress by "Silencing" Central Glucagon-Like Peptide 1 Signaling in Rats
复制标题
DOI：
10.1523/jneurosci.3464-14.2015
复制
发表时间：
2015-07-29
影响因子：
5.3
通讯作者：
Rinaman, Linda
中科院分区：
文献类型：
--
作者：
Maniscalco, James W.;Zheng, Huiyuan;Rinaman, Linda
先前的报告表明，热量限制会减弱焦虑和对急性压力的其他行为反应，并削弱压力增加垂体前叶释放促肾上腺皮质激素的能力。由于后脑胰高血糖素样肽-1 (GLP-1) 神经元和去甲肾上腺素能催乳素释放肽 (PrRP) 神经元参与行为和内分泌应激反应，并且对代谢状态敏感，因此我们检查过夜食物剥夺是否会减弱应激诱导的这些神经元及其下游下丘脑和边缘前脑靶标的募集。在高架十字迷宫和声音惊吓测试中评估的单次过夜快速减少了焦虑样行为，包括光增强惊吓的显着减弱。急性应激[即 30 分钟约束 (RES) 或 5 分钟升高平台暴露]在进食大鼠中强烈激活 GLP-1 和 PrRP 神经元中的 c-Fos，但在禁食大鼠中则不然。禁食还显着削弱了急性应激激活终纹前腹外侧床核 (vlBST) 内 c-Fos 表达的能力。急性 RES 应激抑制了随意喂养的大鼠的黑暗发作食物摄入，而中央输注 GLP-1 受体拮抗剂则可以阻断 RES 诱导的吞咽不足，并降低随意喂养的大鼠中 RES 激活 PrRP 和前 vlBST 神经元的能力。因此，过夜禁食可以“沉默”GLP-1 和 PrRP 神经元，并减少对急性应激的焦虑样反应和食欲减退反应。在 GLP-1 受体拮抗后，对随意喂养的大鼠中这些禁食诱导的效应进行了部分模仿，这表明短期负能量平衡减弱对急性应激的神经内分泌和行为反应的潜在机制。
Previous reports indicate that caloric restriction attenuates anxiety and other behavioral responses to acute stress, and blunts the ability of stress to increase anterior pituitary release of adrenocorticotropic hormone. Since hindbrain glucagon-like peptide-1 (GLP-1) neurons and noradrenergic prolactin-releasing peptide (PrRP) neurons participate in behavioral and endocrine stress responses, and are sensitive to the metabolic state, weexamined whether overnight food deprivation blunts stress-induced recruitment of these neurons and their downstream hypothalamic and limbic forebrain targets. A single overnight fast reduced anxiety-like behavior assessed in the elevatedplus maze and acoustic startle test, including marked attenuation of light-enhanced startle. Acute stress [i.e., 30 min restraint (RES) or 5 min elevated platform exposure] robustly activated c-Fos in GLP-1 and PrRP neurons in fed rats, but not in fasted rats. Fasting also significantly blunted the ability of acute stress to activate c-Fos expression within the anterior ventrolateral bed nucleus of the stria terminalis (vlBST). Acute RES stress suppressed dark-onset food intake in rats that were fed ad libitum, whereas central infusion of a GLP-1 receptor antagonist blocked RES-induced hypophagia, and reduced the ability of RES to activate PrRP and anterior vlBST neurons in ad libitum-fed rats. Thus, an overnight fast "silences" GLP-1 and PrRP neurons, and reduces both anxiety-like and hypophagic responses to acute stress. The partial mimicking of these fasting-induced effects in ad libitum-fed rats after GLP-1 receptor antagonism suggests a potential mechanism by which short-term negative energy balance attenuates neuroendocrine and behavioral responses to acute stress.