Hypothalamic cocaine- and amphetamine-regulated transcript neurons project to areas expressing gonadotropin releasing hormone immunoreactivity and to the anteroventral periventricular nucleus in male and female rats

Cocaine- and amphetamine-regulated transcript (CART) and CART-derived peptides are widely expressed in the hypothalamus. CART is involved in food intake control and is regulated by circulating leptin, a hormone implicated in a variety of endocrine functions. Lack of leptin ( ob/ob mice) is associate...

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Published in:	Neuroscience Vol. 125; no. 3; pp. 735 - 748
Main Authors:	Rondini, T.A, Baddini, S.P, Sousa, L.F, Bittencourt, J.C, Elias, C.F
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 2004 Elsevier
Subjects:	Animals Arcuate Nucleus of Hypothalamus - cytology Arcuate Nucleus of Hypothalamus - metabolism Arcuate Nucleus of Hypothalamus - secretion Biological and medical sciences Biotin - analogs & derivatives Dextrans Estrous Cycle - physiology Female Fluorescent Dyes Fundamental and applied biological sciences. Psychology Gonadotropin-Releasing Hormone - metabolism Gonadotropin-Releasing Hormone - secretion hypothalamus Hypothalamus - cytology Hypothalamus - metabolism Hypothalamus - secretion leptin Leptin - metabolism Male Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Neural Pathways - cytology Neural Pathways - metabolism Neural Pathways - secretion Neurons - cytology Neurons - metabolism preoptic area Preoptic Area - cytology Preoptic Area - metabolism Presynaptic Terminals - metabolism Presynaptic Terminals - secretion Presynaptic Terminals - ultrastructure Proto-Oncogene Proteins c-fos - metabolism Rats Rats, Sprague-Dawley reproduction Reproduction - physiology RNA, Messenger - metabolism Sex Characteristics sexual behavior Stilbamidines Vertebrates: nervous system and sense organs FG PVH LHA OBRb OVLT MPO sexual behavior KPBS Pe GnRH DMH PBS SSC MnPO AVPV MS ir SOCS-3 preoptic area DEPC leptin POMC VMH RCA Arc PMV LH hypothalamus BDA reproduction CART Rat Cocaine amphetamine regulated transcript peptide Rodentia Central nervous system Sexual behavior Gonadotropin RH Male Hypothalamus Encephalon Hypothalamic hormone Vertebrata Reproduction Mammalia Neuron Animal Leptin Female Periventricular nucleus Hormone releasing factor
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Summary:	Cocaine- and amphetamine-regulated transcript (CART) and CART-derived peptides are widely expressed in the hypothalamus. CART is involved in food intake control and is regulated by circulating leptin, a hormone implicated in a variety of endocrine functions. Lack of leptin ( ob/ob mice) is associated with obesity, hypogonadism and infertility. In the arcuate nucleus, dorsomedial nucleus of the hypothalamus, and ventral premammillary nucleus, CART neurons also express leptin receptor long-form splice-variant. Recent studies have suggested that the facilitatory effect of leptin on gonadotropin-releasing hormone (GnRH) secretion is mediated by CART. In the present study, using dual- and triple-label immunohistochemistry, we identified CART fibers in close apposition with GnRH neurons expressing Fos in the afternoon of the proestrous day, as well as with GnRH neurons in male rats. In order to investigate the origin of these fibers, we injected the retrograde tracer Fluorogold into areas containing GnRH cell bodies. In male and female rats, the tracer was injected around the vascular organ of lamina terminalis, median preoptic nucleus and medial preoptic nucleus, as well as in the anteroventral periventricular nucleus. We observed retrogradely labeled neurons in various hypothalamic nuclei, including the arcuate, dorsomedial and ventral premammillary. In these areas, dual-label immunohistochemistry/ in situ hybridization revealed that part of the retrogradely labeled neurons also express CART mRNA. As a control, we injected the anterograde tracer biotinylated dextran amine into the ventral premammillary nucleus of both males and females. Most projections targeted brain areas related to reproductive behavior and few fibers were closely associated with GnRH neurons. Our findings indicate that ventral premammillary nucleus CART neurons intermingle with brain circuitry involved in reproduction. Therefore, these neurons are well positioned to mediate leptin effect on reproductive control.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0306-4522 1873-7544
DOI:	10.1016/j.neuroscience.2003.12.045