title: Efferent projections of neuropeptide Y-expressing neurons of the dorsomedial hypothalamus in chronic hyperphagic models.
abstract: The dorsomedial hypothalamus (DMH) has long been implicated in feeding behavior and thermogenesis. The DMH contains orexigenic neuropeptide Y (NPY) neurons, but the role of these neurons in the control of energy homeostasis is not well understood. NPY expression in the DMH is low under normal conditions in adult rodents but is significantly increased during chronic hyperphagic conditions such as lactation and diet-induced obesity (DIO). To understand better the role of DMH-NPY neurons, we characterized the efferent projections of DMH-NPY neurons using the anterograde tracer biotinylated dextran amine (BDA) in lactating rats and DIO mice. In both models, BDA- and NPY-colabeled fibers were limited mainly to the hypothalamus, including the paraventricular nucleus of the hypothalamus (PVH), lateral hypothalamus/perifornical area (LH/PFA), and anteroventral periventricular nucleus (AVPV). Specifically in lactating rats, BDA-and NPY-colabeled axonal swellings were in close apposition to cocaine- and amphetamine-regulated transcript (CART)-expressing neurons in the PVH and AVPV. Although the DMH neurons project to the rostral raphe pallidus (rRPa), these projections did not contain NPY immunoreactivity in either the lactating rat or the DIO mouse. Instead, the majority of BDA-labeled fibers in the rRPa were orexin positive. Furthermore, DMH-NPY projections were not observed within the nucleus of the solitary tract (NTS), another brainstem site critical for the regulation of sympathetic outflow. The present data suggest that NPY expression in the DMH during chronic hyperphagic conditions plays important roles in feeding behavior and thermogenesis by modulating neuronal functions within the hypothalamus, but not in the brainstem.
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon 97006, USA.
authors.forename: Shin J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Melissa
authors.initials: M
authors.lastname: Kirigiti
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Lindsley
authors.forename: Alberto
authors.initials: A
authors.lastname: Loche
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Madden
authors.forename: Shaun F
authors.initials: SF
authors.lastname: Morrison
authors.forename: M Susan
authors.initials: MS
authors.lastname: Smith
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Grove
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001710:Biotin / Q000031:analogs & derivatives; D002908:Chronic Disease; D003911:Dextrans; D004195:Disease Models, Animal; D004525:Efferent Pathways / Q000378:metabolism* / Q000502:physiology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006963:Hyperphagia / Q000473:pathology*; D007028:Hypothalamic Hormones / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000473:pathology*; D000068797:Orexins; D010446:Peptide Fragments / Q000378:metabolism; D010907:Pituitary Hormones / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D001710:Biotin; D003911:Dextrans; D007987:Gonadotropin-Releasing Hormone; D007028:Hypothalamic Hormones; D047908:Intracellular Signaling Peptides and Proteins; D019344:Lactic Acid; D008543:Melanins; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D010446:Peptide Fragments; D010907:Pituitary Hormones; D014365:Tryptophan Hydroxylase; C076397:biotinylated dextran amine; C428723:cocaine- and amphetamine-regulated transcript protein (55-102); D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; C019463:melanin-concentrating hormone