The temporal and spatial pattern of leptin receptor-expressing cells in the developing mouse hypothalamus

IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Matt B. A. Higgins, Kelly A. Glendining, Christine L. Jasoni
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Abstract

The arcuate nucleus is a crucial hypothalamic brain region involved in regulating body weight homeostasis. Neurons within the arcuate nucleus respond to peripheral metabolic signals, such as leptin, and relay these signals via neuronal projections to brain regions both within and outside the hypothalamus, ultimately causing changes in an animal's behaviour and physiology. There is a substantial amount of evidence to indicate that leptin is intimately involved with the postnatal development of arcuate nucleus melanocortin circuitry. Further, it is clear that leptin signalling directly in the arcuate nucleus is required for circuitry development. However, as leptin receptor long isoform (Leprb) mRNA is expressed in multiple nuclei within the developing hypothalamus, including the postsynaptic target regions of arcuate melanocortin projections, this raises the possibility that leptin also signals in these nuclei to promote circuitry development. Here, we used RT-qPCR and RNAscope® to reveal the spatio-temporal pattern of Leprb mRNA in the early postnatal mouse hypothalamus. We found that Leprb mRNA expression increased significantly in the arcuate nucleus, ventromedial nucleus and paraventricular nucleus of the hypothalamus from P8, in concert with the leptin surge. In the dorsomedial nucleus of the hypothalamus, increases in Leprb mRNA were slightly later, increasing significantly from P12. Using duplex RNAscope®, we found Leprb co-expressed with Sim1, Pou3f2, Mc4r and Bdnf in the paraventricular nucleus at P8. Together, these data suggest that leptin may signal in a subset of neurons postsynaptic to arcuate melanocortin neurons, as well as within the arcuate nucleus itself, to promote the formation of arcuate melanocortin circuitry during the early postnatal period.

Abstract Image

发育中小鼠下丘脑瘦素受体表达细胞的时间和空间模式
弓状核是下丘脑中参与调节体重平衡的重要脑区。弓状核内的神经元对瘦素等外周代谢信号做出反应,并通过神经元投射将这些信号传递到下丘脑内外的脑区,最终导致动物的行为和生理发生变化。大量证据表明,瘦素与弓状核黑色皮质素回路的产后发育密切相关。此外,直接在弓状核中传递瘦素信号显然是电路发育所必需的。然而,由于瘦素受体长异构体(Leprb)mRNA在发育中的下丘脑多个核团中都有表达,包括弓状核黑色素皮质素投射的突触后靶区,这就提出了一种可能性,即瘦素也会在这些核团中发出信号,促进回路发育。在这里,我们利用 RT-qPCR 和 RNAscope® 揭示了小鼠出生后早期下丘脑中 Leprb mRNA 的时空模式。我们发现,从P8开始,Leprb mRNA在下丘脑弓状核、腹内侧核和室旁核的表达显著增加,这与瘦素的激增是一致的。在下丘脑背内侧核,Leprb mRNA的增加稍晚,从P12开始显著增加。利用双链 RNAscope®,我们发现 Leprb 在 P8 时与 Sim1、Pou3f2、Mc4r 和 Bdnf 在室旁核共同表达。这些数据共同表明,瘦素可能会在与弓状黑皮质素神经元突触后的神经元亚群以及弓状核本身发出信号,从而在出生后早期促进弓状黑皮质素回路的形成。
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来源期刊
Journal of Neuroendocrinology
Journal of Neuroendocrinology 医学-内分泌学与代谢
CiteScore
6.40
自引率
6.20%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Journal of Neuroendocrinology provides the principal international focus for the newest ideas in classical neuroendocrinology and its expanding interface with the regulation of behavioural, cognitive, developmental, degenerative and metabolic processes. Through the rapid publication of original manuscripts and provocative review articles, it provides essential reading for basic scientists and clinicians researching in this rapidly expanding field. In determining content, the primary considerations are excellence, relevance and novelty. While Journal of Neuroendocrinology reflects the broad scientific and clinical interests of the BSN membership, the editorial team, led by Professor Julian Mercer, ensures that the journal’s ethos, authorship, content and purpose are those expected of a leading international publication.
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