Differential Level of RXFP3 Expression in Dopaminergic Neurons Within the Arcuate Nucleus, Dorsomedial Hypothalamus and Ventral Tegmental Area of RXFP3-Cre/tdTomato Mice

Frontiers in Neuroscience

Lee D. Hamilton¹  Leni R. Rivera²  Laura Gray²  Lara M. Voglsanger²  Craig M. Smith²  Richard Williams²  Izel M. Eraslan²  Justin Read²  Sarah S. Ch’ng³  Andrew L. Gundlach³  Cary Zhang³ 

[1] Faculty of Health, School of Exercise and Nutritional Science, Deakin University, Waurn Ponds, VIC, Australia;Faculty of Health, School of Medicine, Institute for Innovation in Mental and Physical Health and Clinical Translation, Deakin University, Waurn Ponds, VIC, Australia;The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia;

关键词: RXFP3;    relaxin-3;    dopamine;    tyrosine hydroxylase;    arcuate nucleus;    dorsomedial hypothalamus;   

DOI  :  10.3389/fnins.2020.594818

来源: DOAJ

【 摘 要 】

RXFP3 (relaxin-family peptide 3 receptor) is the cognate G-protein-coupled receptor for the neuropeptide, relaxin-3. RXFP3 is expressed widely throughout the brain, including the hypothalamus, where it has been shown to modulate feeding behavior and neuroendocrine activity in rodents. In order to better characterize its potential mechanisms of action, this study determined whether RXFP3 is expressed by dopaminergic neurons within the arcuate nucleus (ARC) and dorsomedial hypothalamus (DMH), in addition to the ventral tegmental area (VTA). Neurons that express RXFP3 were visualized in coronal brain sections from RXFP3-Cre/tdTomato mice, which express the tdTomato fluorophore within RXFP3-positive cells, and dopaminergic neurons in these areas were visualized by simultaneous immunohistochemical detection of tyrosine hydroxylase-immunoreactivity (TH-IR). Approximately 20% of ARC neurons containing TH-IR coexpressed tdTomato fluorescence, suggesting that RXFP3 can influence the dopamine pathway from the ARC to the pituitary gland that controls prolactin release. The ability of prolactin to reduce leptin sensitivity and increase food consumption therefore represents a potential mechanism by which RXFP3 activation influences feeding. A similar proportion of DMH neurons containing TH-IR expressed RXFP3-related tdTomato fluorescence, consistent with a possible RXFP3-mediated regulation of stress and neuroendocrine circuits. In contrast, RXFP3 was barely detected within the VTA. TdTomato signal was absent from the ARC and DMH in sections from Rosa26-tdTomato mice, suggesting that the cells identified in RXFP3-Cre/tdTomato mice expressed authentic RXFP3-related tdTomato fluorescence. Together, these findings identify potential hypothalamic mechanisms through which RXFP3 influences neuroendocrine control of metabolism, and further highlight the therapeutic potential of targeting RXFP3 in feeding-related disorders.

【 授权许可】

Unknown