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Delineation of a novel direct pathway from the hypothalamic proopiomelanocortin (POMC) neurons projecting to the brainstem raphe pallidus (RPa) melanocortin 4 receptor (MC4R) neurons
Author(s) -
Lei Liugen,
Murphy Jonathan G,
Smart James L,
Low Malcolm J,
Fan Wei
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a460-a
Subject(s) - colocalization , melanocortin , dorsal raphe nucleus , proopiomelanocortin , raphe nuclei , brainstem , arcuate nucleus , neuroscience , medicine , microbiology and biotechnology , biology , chemistry , endocrinology , hypothalamus , receptor , serotonergic , serotonin , hormone
The central melanocortin system plays a critical role in energy homeostasis, but its exact underlying neuronal circuitry remains to be delineated. The RPa and adjacent areas contain sympathetic premotor neurons regulating thermogenesis. We observed, using dual immunocytochemistry (ICC) and MC4R‐sapphire transgenic mice, that α‐MSH‐immunoreactive (IR) fibers were in close apposition to MC4R neurons in the RPa, but no agouti related peptide (AGRP)‐IR fibers were detected in the RPa. To further investigate the origin of the α‐MSH‐IR fibers in the RPa, the retrograde tracer choleratoxin‐b subunit (CTB) was injected into the RPa region in POMC‐EGFP transgenic mice. The injection sites covered the RPa, RMg, parts of ROb and gigantocellular reticular nucleus, α part (n=4). An average of ~16 % colocalization of CTB/POMC‐EGFP‐IR neurons and ~49 % colocalization of POMC‐EGFP‐IR/CTB‐IR neurons were observed in the hypothalamic ARC/RCA. No colocalization of CTB‐IR and POMC‐EGFP‐IR neurons was found in the NTS. These results delineate a novel direct pathway from the hypothalamic POMC neurons projecting to the RPa MC4R neurons, and provide a neuroanatomical basis for the potential functional implication of brainstem RPa MC4R signaling in the regulation of energy balance. Supported by NIH grant DK62179 (WF). We thank Dr. Jeffrey M. Friedman and Dr. Hongyan Liu for provision of MC4R and NPY‐sapphire transgenic mice.