Maturation of the hypothalamic arcuate agouti-related protein system during postnatal development in the mouse

Maturation of the hypothalamic arcuate agouti-related protein system during postnatal development in the mouse
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DOI:
10.1016/j.devbrainres.2005.01.009
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发表时间:
2005-03-31
期刊:
DEVELOPMENTAL BRAIN RESEARCH
影响因子:
--
通讯作者:
Fetissov, SO
Fetissov, SO
中科院分区:
其他
文献类型:
--
作者:
Nilsson, I;Johansen, JE;Fetissov, SO

文献摘要

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下丘脑弓状核(Arc)及其表达刺鼠相关蛋白(AgRP)的神经元是参与能量稳态长期调节的前脑回路的关键组成部分,包括将瘦素信号传递到下丘脑和下丘脑外区域。在目前的工作中,我们研究了出生后的发展(P0,P5,P10,P15,和P21),该系统(AgRP转录和肽)在小鼠大脑中使用原位杂交和免疫组织化学。在所有阶段,AgRP mRNA的表达只在弧检测。在P0,AgRP mRNA水平低,只有少数AgRP免疫反应纤维存在到达,吻侧,终纹床核,尾侧,中缝背核。在随后的时期(P5-P21),AgRP mRNA的水平逐渐增加,在弧沿着的AgRP纤维密度的增加,在下丘脑区域负责控制食欲,包括室旁核,以及在下丘脑外区域,包括蓝斑。这些数据提供的证据表明,在小鼠中,AgRP弧系统的成熟主要发生在出生后的前三周。结合食欲和体重生理学的现有数据,我们的数据表明,小鼠出生后的前三周是通过外周激素形成食欲控制的大脑机制的关键时期。(c)2005 Elsevier B. V.保留所有权利。
The hypothalamic arcuate nucleus (Arc) and its neurons expressing agouti-related protein (AgRP) are key components of the forebrain circuitry involved in long-term regulation of energy homeostasis, including conveying leptin signaling to other hypothalamic and extrahypothalamic regions. In the present work, we investigated the postnatal development (P0, P5, P10, P15, and P21) of this system (AgRP transcript and peptide) in the mouse brain using in situ hybridization and immunohistochemistry. At all stages, AgRP mRNA expression was detected exclusively in the Arc. At P0, AgRP mRNA levels were low, and only a few AgRP-immunoreactive fibers were present reaching, rostrally, the bed nucleus of the stria terminalis and, caudally, the dorsal raphe nucleus. During the following period (P5-P21), the levels of AgRP mRNA gradually increased in the Arc along with a parallel increase in the AgRP fiber density in the hypothalamic regions responsible for control of appetite, including the paraventricular nucleus, as well as in extrahypothalamic regions, including locus coeruleus. These data provide evidence that, in the mouse, the maturation of the AgRP Arc system occurs mainly during the first three postnatal weeks. Together with the existing data on the physiology of appetite and body weight, our data suggest that the first three postnatal weeks in the mouse represents a critical period for the formation of brain mechanisms underlying appetite control via peripheral hormones. (c) 2005 Elsevier B.V. All rights reserved.