Distribution and neurochemical characterization of neurons within the nucleus of the solitary tract responsive to serotonin agonist-induced hypophagia.
Distribution and neurochemical characterization of neurons within the nucleus of the solitary tract responsive to serotonin agonist-induced hypophagia.
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DOI：
10.1016/j.bbr.2008.07.039
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发表时间：
2009-01-03
影响因子：
2.7
通讯作者：
Heisler, Lora K.
中科院分区：
文献类型：
--
作者：
Lam, Daniel D.;Zhou, Ligang;Vegge, Andreas;Xiu, Philip Y.;Christensen, Britt T.;Osundiji, Mayowa A.;Yueh, Chen-yu;Evans, Mark L.;Heisler, Lora K.
增强肾上腺素能紧张的药理学化合物显著减少食物摄入，并且是肥胖症的最临床有效的治疗方法之一。然而，中枢机制，通过它的多巴胺能化合物调节摄食行为尚未完全确定。在中枢神经系统中，接受内脏胃肠信息的主要中继中枢是尾侧脑干的孤束核（NTS）。在这里，我们研究了经典的厌食症5-羟色胺受体激动剂间氯苯基哌嗪（mCPP）是否增强代谢敏感的NTS神经元的活性。使用c-fos免疫反应（FOS-IR）作为神经元激活的标记物在大鼠，我们观察到mCPP显着和剂量依赖性激活的离散群体的尾侧NTS神经元的最后区（AP）的水平。特别是，FOS-IR诱导的这种模式与含儿茶酚胺神经元的位置一致。用FOS-IR和儿茶酚胺生物合成酶酪氨酸羟化酶（TH）进行的双标记显示，在AP水平，mCPP在NTS中83.7%的含TH-IR的神经元中诱导FOS-IR。TH神经元的激活程度与摄食量呈显著负相关。此外，这种激活是特定的儿茶酚胺神经元，可卡因和安非他明调节转录（CART），胆囊收缩素（CCK），胰高血糖素样肽1（GLP-1），或神经降压素神经元的诱导可以忽略不计。NTS儿茶酚胺能神经元将内脏胃肠信号传递到下丘脑外侧核（LHA）和室旁核（PVH），在那里这些信号被整合到调节食物摄入的自主神经和激素反应中。这里提供的数据确定了一种新的机制，通过该机制，5-羟色胺受体激动剂在尾脑干中起作用，可以调节摄食行为。
Pharmacological compounds enhancing serotonergic tone significantly decrease food intake and are among the most clinically efficacious treatments for obesity. However, the central mechanisms through which serotonergic compounds modulate feeding behavior have not been fully defined. The primary relay center receiving visceral gastrointestinal information in the central nervous system is the nucleus of the solitary tract (NTS) in the caudal brainstem. Here we investigated whether the classic anorectic serotonin receptor agonist m-chloro-phenylpiperazine (mCPP) enhances the activity of metabolically sensitive NTS neurons. Using c-fos immunoreactivity (FOS-IR) as a marker of neuronal activation in rats, we observed that mCPP significantly and dose-dependently activated a discrete population of caudal NTS neurons at the level of the area postrema (AP). In particular, this pattern of FOS-IR induction was consistent with the location of catecholamine-containing neurons. Dual-labeling performed with FOS-IR and the catecholamine biosynthetic enzyme tyrosine hydroxylase (TH) revealed that mCPP induced FOS-IR in 83.7% of TH-IR containing neurons in the NTS at the level of the AP. The degree of activation of TH neurons was strongly negatively correlated with food intake. Moreover, this activation was specific to catecholamine neurons, with negligible induction of cocaine- and amphetamine-regulated transcript (CART), cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), or neurotensin neurons. NTS catecholaminergic neurons relay visceral gastrointestinal signals to both the lateral hypothalamus (LHA) and paraventricular nucleus of the hypothalamus (PVH), where these signals are integrated into autonomic and hormonal responses regulating food intake. The data presented here identify a novel mechanism through which a serotonin receptor agonist acting in the caudal brainstem may regulate ingestive behavior.
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影响因子：
5
作者：
GLENNON, RA;ISMAIEL, AEM;PEROUTKA, SJ
通讯作者：
PEROUTKA, SJ
影响因子：
3.4
作者：
Grill, HJ;Donahey, JCK;Kaplan, JM
通讯作者：
Kaplan, JM
影响因子：
2.5
作者：
MANAKER, S;VERDERAME, HM
通讯作者：
VERDERAME, HM
影响因子：
3.4
作者：
Rowland, NE;Robertson, K;Rema, E
通讯作者：
Rema, E
影响因子：
3.4
作者：
KITCHENER, SJ;DOURISH, CT
通讯作者：
DOURISH, CT