Hindbrain GLP-1 receptor mediation of cisplatin-induced anorexia and nausea.
Hindbrain GLP-1 receptor mediation of cisplatin-induced anorexia and nausea.
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DOI：
10.1016/j.physbeh.2015.10.031
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发表时间：
2016-01-01
影响因子：
2.9
通讯作者：
Hayes MR
中科院分区：
文献类型：
--
作者：
De Jonghe BC;Holland RA;Olivos DR;Rupprecht LE;Kanoski SE;Hayes MR
虽然化疗诱导的恶心和呕吐在治疗后的急性期（<24小时）在临床上得到控制，但在化疗的延迟期（> 24小时）期间，厌食、恶心、疲劳和其他疾病型行为在很大程度上不受控制。由于后脑胰高血糖素样肽-1（GLP-1）系统有助于能量平衡并介导厌恶和应激刺激，因此我们在此研究了以下假设：后脑GLP-1信号传导介导大鼠化疗诱导的恶心和进食行为减少。具体而言，通过第4次脑室内（ICV）毒蜥外泌肽-（9-39）注射进行的后脑GLP-1受体（GLP-1 R）阻断可减轻顺铂化疗在化疗诱导的恶心延迟期（48小时）引起的厌食、体重减轻和异食癖（恶心诱导的高岭土摄入）。此外，本数据提供的证据表明，尾侧脑干孤束核（NTS）中的中枢GLP-1产生前胰高血糖素原神经元在化疗诱导的恶心延迟期被顺铂激活，因为顺铂导致NTS GLP-1免疫反应性神经元中的c-Fos免疫反应性显著增加。这些数据支持越来越多的文献，表明中枢GLP-1系统可能是用于治疗化疗治疗伴随的恶心和呕吐、厌食和体重减轻延迟相的辅助止吐药的潜在药物靶点。
While chemotherapy-induced nausea and vomiting is clinically controlled in the acute (<24h) phase following treatment, the anorexia, nausea, fatigue, and other illness-type behaviors during the delayed phase (>24h) of chemotherapy are largely uncontrolled. As the hindbrain glucagon-like peptide-1 (GLP-1) system contributes to energy balance and mediates aversive and stressful stimuli, here we examine the hypothesis that hindbrain GLP-1 signaling mediates aspects of chemotherapy-induced nausea and reductions in feeding behavior in rats. Specifically, hindbrain GLP-1 receptor (GLP-1R) blockade, via 4th intracerebroventricular (ICV) exendin-(9-39) injections, attenuates the anorexia, body weight reduction, and pica (nausea-induced ingestion of kaolin clay) elicited by cisplatin chemotherapy during the delayed phase (48hr) of chemotherapy-induced nausea. Additionally, the present data provide evidence that the central GLP-1-producing preproglucagon neurons in the nucleus tractus solitarius (NTS) of the caudal brainstem are activated by cisplatin during the delayed phase of chemotherapy-induced nausea, as cisplatin led to a significant increase in c-Fos immunoreactivity in NTS GLP-1-immunoreactive neurons. These data support a growing body of literature suggesting that the central GLP-1 system may be a potential pharmaceutical target for adjunct anti-emetics used to treat the delayed-phase of nausea and emesis, anorexia, and body weight loss that accompany chemotherapy treatments.