首页> 外文期刊>American Journal of Physiology >Neurochemical phenotype of hypothalamic neurons showing Fos expression 23 h after intracranial AgRP.
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Neurochemical phenotype of hypothalamic neurons showing Fos expression 23 h after intracranial AgRP.

机译:下丘脑神经元的神经化学表型显示颅内AgRP后23 h Fos表达。

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Agouti-related protein (AgRP) is coexpressed with neuropeptide Y (NPY) in a population of neurons in the arcuate nucleus (ARC) of the hypothalamus and stimulates food intake for up to 7 days if injected intracerebroventricularly. The prolonged food intake stimulation does not seem to depend on continued competition at the melanocortin-4 receptor (MC4R), because the relatively specific MC4R agonist MTII regains its ability to suppress food intake 24 h after AgRP injection. Intracerebroventricular AgRP also stimulates c-Fos expression 24 h after injection in several brain areas, so the neurons exhibiting delayed Fos expression might be particularly important in feeding behavior. Thus we aimed to identify the neurochemical phenotype of some of these neurons in select hypothalamic areas, using double-label immunohistochemistry. AgRP-injected rats ingested significantly more chow (10.2 +/- 0.6 g) vs. saline controls (3.4 +/- 0.7 g) in the first 9 h (light phase) after injection. In the lateral hypothalamus (particularly the perifornical area) 23 h after injection, AgRP induced significantly more Fos vs. saline in orexin-A (OXA) neurons (25.6 +/- 4.9 vs. 4.8 +/- 3.1%), but not in melanin-concentrating hormone (MCH) or cocaine- and amphetamine-regulated transcript (CART) neurons. In the ARC, AgRP induced significantly more Fos in CART (40.6 +/- 5.9 vs. 13.4 +/- 1.8%) but not NPY neurons. In the paraventricular nucleus, there was no significant difference in Fos expression induced by AgRP vs. saline in oxytocin and CART neurons. We conclude that the long-lasting hyperphagia induced by AgRP is correlated with and possibly partially mediated by hyperactive OXA neurons in the lateral hypothalamus and CART neurons in the ARC, but not by NPY and MCH neurons. The substantial increase in light-phase food intake by AgRP supports a role for the arousing effects of OXA. Activation of CART neurons in the ARC (which likely coexpress proopiomelanocortin) could indicate attempts to activate counterregulatory decreases in food intake.
机译:在下丘脑弓状核(ARC)的神经元群体中,刺痛相关蛋白(AgRP)与神经肽Y(NPY)共表达,如果脑室内注射,刺激食物摄取长达7天。延长的食物摄取刺激似乎并不取决于在melanocortin-4受体(MC4R)上的持续竞争,因为相对特异性的MC4R激动剂MTII在注射AgRP后24小时恢复了抑制食物摄取的能力。注射后24 h,脑室内AgRP还刺激几个脑区域的c-Fos表达,因此表现出延迟Fos表达的神经元在进食行为中可能特别重要。因此,我们旨在使用双标记免疫组化技术来鉴定某些下丘脑区域中某些神经元的神经化学表型。注射AgRP的大鼠在注射后的前9小时(轻度阶段)与盐水对照组(3.4 +/- 0.7 g)相比,摄取了更多的食物(10.2 +/- 0.6 g)。注射后23小时,在下丘脑外侧区(尤其是在穹n区),AgRP在食欲素A(OXA)神经元中诱导的Fos与盐水相比明显增加(25.6 +/- 4.9与4.8 +/- 3.1%),而在黑色素浓缩激素(MCH)或可卡因和苯丙胺调节的转录(CART)神经元。在ARC中,AgRP诱导CART中的Fos明显增加(40.6 +/- 5.9对13.4 +/- 1.8%),而不是NPY神经元。在脑室旁核中,催产素和CART神经元中由AgRP诱导的Fos表达与盐水诱导的Fos表达没有显着差异。我们得出的结论是,AgRP诱导的长期食欲亢进与外侧下丘脑中的过度活跃的OXA神经元和ARC中的CART神经元相关,并可能部分介导,而与NPY和MCH神经元无关。 AgRP显着增加了光相食物的摄入,这有助于OXA的激发作用。 ARC中CART神经元的激活(可能共表达proopiomelanocortin)可能表明试图激活食物摄入量反调节的减少。

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