Relationship of alpha-MSH and AgRP axons to the perikarya of melanocortin-4 receptor neurons

Autor(es)

Lima, Leandro B. ^[1] ; Pedroso, Joao A. B. ^[1] ; Metzger, Martin ^[1] ; Gautron, Laurent ^[2] ; Donato, Jr., Jose ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, Sao Paulo, SP - Brazil

^[2] Univ Texas Southwestern Med Ctr Dallas, Div Hypothalam Res, Dept Internal Med, Dallas, TX 75390 - USA

• Tipo de documento: Artigo Científico
• Fonte: Brain Research; v. 1717, p. 136-146, AUG 15 2019.
• Citações Web of Science: 0

Resumo

The central melanocortin system is composed of neurons that express either the proopiomelanocortin (POMC) or the agouti-related protein (AgRP). POMC is cleaved in bioactive peptides, including the alpha-melanocyte-stimulating hormone (alpha-MSH). alpha-MSH activates the melanocortin-4 receptor (MC4R) inducing satiety, whereas AgRP acts as an inverse agonist of MC4R. However, only limited information is available regarding possible area-specific differences in the interaction between alpha-MSH and AgRP terminals on MC4R-expressing cells. Therefore, the objective of the present study was to compare the distribution pattern of alpha-MSH and AgRP terminals on the perikarya of MC4R-expressing neurons. We performed a triple-label immunofluorescence reaction in brain series of MC4R-reporter mice to visualize MC4R-expressing neurons together with AgRP and a-MSH terminals. POMC and AgRP neurons project to areas that contain MC4R-expressing cells, although several brain nuclei exhibit AgRP and alpha-MSH terminals, but they do no express MC4R, while other brain areas contain MC4R-expressing cells and receive no apparent innervation of AgRP and POMC neurons. AgRP terminals make more presumptive appositions than a-MSH on the soma of MC4R-expressing neurons of the medial preoptic area and paraventricular nucleus of the hypothalamus (Pa). Additionally, a higher percentage of MC4R cells receive at least one presumptive apposition from AgRP terminals in the median preoptic nucleus and Pa, compared to alpha-MSH appositions. Thus, our study revealed area-specific differences in the interaction between alpha-MSH and AgRP terminals and the soma of MC4R-expressing neurons. These findings provide new insights about the relationship between first- and second-order neurons of the central melanocortin system. (AU)

• Processo FAPESP: 17/02983-2 - Ação do hormônio do crescimento no sistema nervoso: relevância para as funções neurais e na doença
• Beneficiário: Jose Donato Junior
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/16473-6 - Processamento de estímulos aversivos: circuitaria entre o núcleo tegmental laterodorsal, a habênula, e os núcleos dorsal e mediano da rafe
• Beneficiário: Martin Andreas Metzger
• Linha de fomento: Auxílio à Pesquisa - Regular