Galanin-like peptide promotes feeding behaviour via activation of orexinergic neurones in the rat lateral hypothalamus

Galanin-like peptide promotes feeding behaviour via activation of orexinergic neurones in the rat lateral hypothalamus
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DOI:
10.1111/j.1365-2826.2005.01382.x
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发表时间:
2006-01-01
影响因子:
3.2
通讯作者:
Shioda, S
Shioda, S
中科院分区:
医学3区
文献类型:
--
作者:
Kageyama, H;Kita, T;Shioda, S

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甘丙肽样肽(GALP)产生于下丘脑弓状核的神经元中,并与摄食行为的神经控制有关。在此之前,我们已经报道了GALP免疫反应纤维直接接触食欲素/下丘脑泌素免疫反应神经元在大鼠下丘脑外侧使用双免疫荧光。已知中央给药GALP可刺激摄食行为。然而,该动作的目标神经元尚未明确。本研究的目的是确定在大鼠的GALP介导的神经元摄食途径的特点。因此,在超微结构水平上,发现GALP免疫反应轴突终末在下丘脑外侧区的食欲素/下丘脑泌素免疫反应细胞体和树突状突起上形成突触。c-Fos免疫反应性表达在食欲素/下丘脑泌素免疫反应性神经元,但在黑色素浓集的免疫反应性神经元在90分钟后,在外侧下丘脑GALP通过i. c. v.输注的应用。此外,为了确定GALP是否通过食欲素/下丘脑泌素神经元调节进食行为,在有或没有抗食欲素A和B免疫球蛋白(IgG)预处理的情况下,研究了GALP i. c. v.注射后大鼠的进食行为。抗食欲素IgG显著抑制GALP诱导的摄食过多。这些结果表明,食欲素/下丘脑分泌素的神经元在外侧下丘脑的GALP的目标,和GALP诱导的摄食过多介导的食欲素/下丘脑分泌素神经元在大鼠下丘脑。
Galanin-like peptide (GALP) is produced in neurones in the hypothalamic arcuate nucleus and is implicated in the neural control of feeding behaviour. Previously, we have reported that GALP immunoreactive fibres were in direct contact with orexin/hypocretin immunoreactive neurones in the rat lateral hypothalamus using double-immunofluorescence. Centrally administered GALP is known to stimulate feeding behaviour. However, the target neurones of this action have not been clarified. The present study aimed to determine features of the GALP-mediated neuronal feeding pathway in rat. Accordingly, at the ultrastructural level, GALP-immunoreactive axon terminals were found to make synapses on orexin/hypocretin immunoreactive cell bodies and dendritic processes in the lateral hypothalamus. c-Fos immunoreactivity was expressed in orexin/hypocretin-immunoreactive neurones but not in melanin concentrating hormone-immunoreactive neurones in the lateral hypothalamus at 90 min after the application of GALP by i.c.v. infusion. Furthermore, to determine whether GALP regulates feeding behaviour via orexin/hypocretin neurones, the feeding behaviour of rats was studied following GALP i.c.v. injection with or without anti-orexin A and B immunoglobulin (IgG) pretreatment. The anti-orexin IgGs markedly inhibited GALP-induced hyperphagia. These results suggest that orexin/hypocretin-containing neurones in the lateral hypothalamus are targeted by GALP, and that GALP-induced hyperphagia is mediated via orexin/hypocretin neurones in the rat hypothalamus.