Expression of phosphorylated cyclic AMP response element-binding protein in melanin-concentrating hormone neurons and orexin neurons in male and female rats during ad-libitum feeding

Expression of phosphorylated cyclic AMP response element-binding protein in melanin-concentrating hormone neurons and orexin neurons in male and female rats during ad-libitum feeding
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DOI:
10.1097/wnr.0000000000000172
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发表时间:
2014-07-09
期刊:
影响因子:
1.7
通讯作者:
Funabashi, Toshiya
Funabashi, Toshiya
中科院分区:
医学4区
文献类型:
--
作者:
Fukushima, Atsushi;Hagiwara, Hiroko;Funabashi, Toshiya

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利用磷酸化的环AMP反应元件结合蛋白(pCREB)作为神经活动的标志物,我们先前提出食欲素神经元和黑色素浓缩激素(MCH)神经元在摄食行为中发挥不同的作用。在本研究中,我们检测了pCREB在自由摄食过程中的表达;以前,只对禁食的动物进行检查。MCH神经元在自发进食过程中表达pCREB,而不表达促食素神经元。诱导pCREB表达没有性别差异,但衰减似乎在女性比男性更快。根据本研究的结果,我们推测MCH神经元对营养相关的摄食有反应,但摄食素的摄食相关活动并不明显,除非饥饿伴随着压力,例如禁食情况下缺乏食物引起的压力。因此,在正常情况下,吃东西的欲望不会驱动食欲素神经元,但它会驱动MCH神经元。我们通过研究摄入葡萄糖或糖精(一种非代谢甜味剂)对禁食的雄性和雌性大鼠的影响来验证这一假设。葡萄糖和糖精对降低雌性大鼠食欲素神经元中pCREB的表达同样有效。在MCH神经元中,葡萄糖降低了pCREB的表达,而糖精对pCREB的表达没有影响。综上所述,结果表明MCH和食欲素肽在摄食行为中发挥着不同的生理作用。
Using phosphorylated cyclic AMP response element-binding protein (pCREB) as a marker of neural activity, we previously suggested that orexin neurons and melanin-concentrating hormone (MCH) neurons play distinct roles in feeding behavior. In the present study, we examined the expression of pCREB during ad-libitum feeding; previously, only fasted animals were examined. MCH neurons, but not orexin neurons, expressed pCREB during spontaneous food intake. The induction of pCREB expression did not differ by sex, but attenuation seemed to occur faster in females than in males. On the basis of the results of the present study, we speculate that MCH neurons respond to nutrition-related feeding, but the feeding-related activity of orexin was not evident unless hunger was accompanied by stress, such as the stress caused by the absence of food in the case of fasting. Therefore, the desire to eat under normal conditions does not drive orexin neurons, but it does drive MCH neurons. We tested this hypothesis by examining the effects of consuming glucose or saccharin, a nonmetabolized sweetener, in fasted male and female rats. Glucose and saccharin were equally effective in reducing pCREB expression in the orexin neurons of female rats. In MCH neurons, glucose attenuated the expression of pCREB, but saccharin had no effect, irrespective of sex. Taken together, the results indicate that MCH and orexin peptides play physiologically distinct roles in feeding behavior.