title: Origin of cocaine- and amphetamine-regulated transcript-containing axons innervating hypophysiotropic corticotropin-releasing hormone-synthesizing neurons in the rat.
abstract: Cocaine- and amphetamine-regulated transcript (CART) has stimulatory effects on the hypothalamic-pituitary-adrenal axis through direct effects on hypophysiotropic CRH neurons. Recently CART-containing axons have been demonstrated to densely innervate the hypophysiotropic CRH neurons. Based on the sources of the CART-immunoreactive (IR) innervation of the paraventricular nucleus, the putative origins of these CART-containing fibers include neurons of the hypothalamic arcuate nucleus that coexpress alphaMSH and medullary adrenaline-producing neurons. To determine whether these cell groups contribute to the CART innervation of the hypophysiotropic CRH neurons, we performed a quadruple-labeling immunofluorescent study using antisera against CRH, CART, alphaMSH, and phenylethanolamine-N-methyl-transferase (PNMT), the latter as a marker for adrenaline. Consistent with previous observations, PNMT- and CART-IR axons densely innervated all CRH neurons, whereas the alphaMSH-IR innervation was sparse. Although approximately 60% of CART-IR varicosities in juxtaposition to CRH neurons cocontained PNMT, only approximately 18% of them were immunopositive for alphaMSH. All alphaMSH-IR boutons and approximately 90% of PNMT-containing varicosities on the surface of CRH neurons were also labeled for CART. The remaining 22% of CART axon varicosities in contact with CRH neurons contained neither alphaMSH nor PNMT. These results indicate that medullary adrenergic/CART neurons are the major source for the CART innervation of CRH neurons in the paraventricular nucleus; however, to a lesser extent the arcuate nucleus also contributes to the CART-IR innervation of these neurons. The observation that nearly 20% of the CART-IR afferents contain neither alphaMSH nor PNMT, however, suggests that additional sources also contribute to the CART-IR input of hypophysiotropic CRH neurons.
authors.affiliation: Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1083, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Wittmann
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Liposits
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Lechan
authors.forename: Csaba
authors.initials: C
authors.lastname: Fekete
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism; D001369:Axons / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis* / Q000502:physiology; D005455:Fluorescent Antibody Technique; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000378:metabolism; D008780:Methyltransferases; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D050918:Phosphatidylethanolamine N-Methyltransferase; D010913:Pituitary-Adrenal System / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D000521:alpha-MSH / Q000378:metabolism; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D000521:alpha-MSH; D003346:Corticotropin-Releasing Hormone; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase