Endogenous GLP-1 in lateral septum contributes to stress-induced hypophagia.
Endogenous GLP-1 in lateral septum contributes to stress-induced hypophagia.
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DOI：
10.1016/j.physbeh.2018.03.001
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发表时间：
2018-08-01
影响因子：
2.9
通讯作者：
Williams DL
中科院分区：
文献类型：
--
作者：
Terrill SJ;Maske CB;Williams DL
尾部脑干的胰高血糖素样肽 1 (GLP-1) 神经元投射到许多大脑区域，包括侧隔膜 (LS)，其在应激反应中具有已知的作用。此前，我们发现LS中的内源性GLP-1在非应激条件下的摄食控制中发挥生理作用，然而，中枢GLP-1也参与对应激的行为和内分泌反应。在这里，我们询问 LS GLP-1 受体 (GLP-1R) 是否会导致应激性吞咽功能减退。雄性大鼠被植入针对 LS 背侧亚区域 (dLS) 的双侧插管。在受试者内部设计中，在黑暗期开始前不久，大鼠在 30 分钟的束缚应激之前接受 dLS 注射盐水或 GLP-1R 拮抗剂 Exendin (9-39) (Ex9)。在接下来的 20 小时内连续测量食物摄入量。在黑暗的前 30 分钟内观察到的压力诱发的吞咽不足不受 Ex9 预处理的影响，但 Ex9 往往会在进入黑暗阶段的 1 和 2 小时内减弱压力的影响。到 4-6 小时，出现了显着的应激 X 药物相互作用，Ex9 预处理阻断了应激诱导的摄食抑制。这些影响完全是通过平均膳食量的变化来调节的。压力抑制了膳食量，而 dLS Ex9 减弱了这种影响。使用类似的设计，我们研究了 dLS GLP-1R 在急性束缚应激的神经内分泌反应中的作用。正如预期的那样，压力会显着增加血清皮质酮，但 dLS GLP-1R 的阻断并不影响这种反应。总之，这些数据表明，dLS 中的内源性 GLP-1 作用在对急性应激的部分但不是全部生理反应中发挥作用。
Glucagon-like peptide 1 (GLP-1) neurons of the caudal brainstem project to many brain areas, including the lateral septum (LS), which has a known role in stress responses. Previously, we showed that endogenous GLP-1 in the LS plays a physiologic role in the control of feeding under non-stressed conditions, however, central GLP-1 is also involved in behavioral and endocrine responses to stress. Here, we asked whether LS GLP-1 receptors (GLP-1R) contribute to stress-induced hypophagia. Male rats were implanted with bilateral cannulas targeting the dorsal subregion of the LS (dLS). In a within-subjects design, shortly before the onset of the dark phase, rats received dLS injections of saline or the GLP-1R antagonist Exendin (9-39) (Ex9) prior to 30 min restraint stress. Food intake was measured continuously for the next 20 h. The stress-induced hypophagia observed within the first 30 minutes of dark was not influenced by Ex9 pretreatment, but Ex9 tended to blunt the effect of stress as early as 1 and 2 h into the dark phase. By 4–6 h, there were significant stress X drug interactions, and Ex9 pretreatment blocked the stress-induced suppression of feeding. These effects were mediated entirely through changes in average meal size; stress suppressed meal size while dLS Ex9 attenuated this effect. Using a similar design, we examined the role of dLS GLP-1R in the neuroendocrine response to acute restraint stress. As expected, stress potently increased serum corticosterone, but blockade of dLS GLP-1Rs did not affect this response. Together, these data show that endogenous GLP-1 action in the dLS plays a role in some but not all of the physiologic responses to acute stress.
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DOI：
10.1038/npp.2010.213
发表时间：
2011-03
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
DOI：
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发表时间：
2011-07-15
期刊：
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影响因子：
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作者：
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通讯作者：
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影响因子：
1.7
作者：
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影响因子：
3.3
作者：
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通讯作者：
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影响因子：
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