Caudal brainstem processing is sufficient for behavioral, sympathetic, and parasympathetic responses driven by peripheral and hindbrain glucagon-like-peptide-1 receptor stimulation
Caudal brainstem processing is sufficient for behavioral, sympathetic, and parasympathetic responses driven by peripheral and hindbrain glucagon-like-peptide-1 receptor stimulation
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DOI：
10.1210/en.2007-1743
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发表时间：
2008-08-01
期刊：
影响因子：
4.8
通讯作者：
Grill, Harvey J.
中科院分区：
文献类型：
--
作者：
Hayes, Matthew R.;Skibicka, Karolina P.;Grill, Harvey J.
外周胰高血糖素样肽-1受体（GLP-1 R）刺激对摄食、胃排空和能量反应的影响涉及迷走神经传递和中枢神经系统处理。尽管缺乏旨在确定哪些中枢神经系统区域对GLP-1 R反应产生至关重要的研究，但认为下丘脑/前脑加工对这些作用至关重要。在此，通过比较慢性丘上去脑（CD）大鼠与成对喂养的完整对照大鼠的反应，评估了尾侧脑干对GLP-1 R激动剂exendin-4（Ex-4）外周给药产生的摄食量、核心温度、心率和胃排空反应控制的贡献。还评价了由Ex-4的后脑脑室内（第四icv）递送驱动的反应。腹膜内Ex-4（1.2和3.0 μ g/kg）抑制了CD大鼠的葡萄糖摄入（摄入5.0 +/- 1.2和4.4 +/- 1.1 ml）和对照品（摄入9.4 +/- 1.5和7.7 +/- 0.8 ml），与溶媒注射后的摄入量（分别摄入13.1 +/- 2.5和13.2 +/- 1.7 ml）相比。与溶剂摄入量（分别为9.3 +/- 2.1和19.3 +/- 4.3 ml）相比，后脑心室Ex-4（0.3 μ g）也抑制了CD大鼠（摄入4.7 +/- 0.6 ml）和对照组（摄入11.0 +/- 2.9 ml）的摄食量。腹膜内Ex-4（0.12、1.2、2.4 μ g/ kg）以剂量相关方式降低CD和对照大鼠的胃排空率。在清醒的行为对照组（0.6和1.0 ℃平均抑制）和CD大鼠（1.5和2.5 ℃平均抑制）中，在ip和第四次icv Ex-4后出现低温。腹膜内Ex-4在对照组和CD大鼠中都引发了心动过速。结果表明，尾侧脑干处理足以介导对摄入、核心温度和胃排空率的抑制以及由外周GLP-1 R激活和后脑递送配体触发的心动过速。与文献相反，观察到的反应不需要下丘脑/前脑处理和前脑-尾脑干通信。
The effects of peripheral glucagon like peptide-1 receptor (GLP-1R) stimulation on feeding, gastric emptying, and energetic responses involve vagal transmission and central nervous system processing. Despite a lack of studies aimed at determining which central nervous system regions are critical for the GLP-1R response production, hypothalamic/forebrain processing is regarded as essential for these effects. Here the contribution of the caudal brainstem to the control of food intake, core temperature, heart rate, and gastric emptying responses generated by peripheral delivery of the GLP-1R agonist, exendin-4 (Ex-4), was assessed by comparing responses of chronic supracollicular decerebrate (CD) rats to those of pair-fed intact control rats. Responses driven by hindbrain intracerebroventricular (fourth icv) delivery of Ex-4 were also evaluated. Intraperitoneal Ex-4 (1.2 and 3.0 mu g/kg) suppressed glucose intake in both CD rats (5.0 +/- 1.2 and 4.4 +/- 1.1 ml ingested) and controls (9.4 +/- 1.5 and 7.7 +/- 0.8 ml ingested), compared with intakes after vehicle injections (13.1 +/- 2.5 and 13.2 +/- 1.7 ml ingested, respectively). Hindbrain ventricular Ex-4 (0.3 mu g) also suppressed food intake in CD rats (4.7 +/- 0.6 ml ingested) and controls (11.0 +/- 2.9 ml ingested), compared with vehicle intakes (9.3 +/- 2.1 and 19.3 +/- 4.3 ml ingested, respectively). Intraperitoneal Ex-4 (0.12, 1.2, 2.4 mu g/ kg) reduced gastric emptying rates in a dose-related manner similarly for both CD and control rats. Hypothermia followed ip and fourth icv Ex-4 in awake, behaving controls (0.6 and 1.0 C average suppression) and CD rats (1.5 and 2.5 C average suppression). Intraperitoneal Ex-4 triggered tachycardia in both control and CD rats. Results demonstrate that caudal brainstem processing is sufficient for mediating the suppression of intake, core temperature, and gastric emptying rates as well as tachycardia triggered by peripheral GLP-1R activation and also hindbrain-delivered ligand. Contrary to the literature, hypothalamic/forebrain processing and forebrain-caudal brainstem communication is not required for the observed responses.