Characterization of CART neurons in the rat and human hypothalamus

Carol F. Elias, Charlotte E. Lee, Joseph F. Kelly, Rexford S. Ahima, Michael Kuhar, Clifford B. Saper, Joel K. Elmquist

Research output: Contribution to journalArticle

315 Citations (Scopus)

Abstract

Cocaine- and amphetamine-regulated transcript (CART) is a recently described neuropeptide widely expressed in the rat brain. CART mRNA and peptides are found in hypothalamic sites such as the paraventricular nucleus (PVH), the supraoptic nucleus (SON), the lateral hypothalamic area (LHA), the dorsomedial nucleus of the hypothalamus (DMH), the arcuate nucleus (Arc), the periventricular nucleus (Pe), and the ventral premammillary, nucleus (PMV). Intracerebroventricular administration of recombinant CART peptide decreases food intake and CART mRNA levels in the Arc are regulated by leptin. Leptin administration induces Fos expression in hypothalamic CART neurons in the PVH, the DMH, the Arc, and the PMV. In the current study, we used double label in situ hybridization histochemistry to investigate the potential direct action of leptin on hypothalamic CART neurons and to define the chemical identity of the hypothalamic CART neurons in the rat brain. We found that CART neurons in the Arc, DMH, and PMV express long form leptin-receptor mRNA, and the suppressor of cytokine signaling-3 (SOCS-3) mRNA after an acute dose of intravenous leptin. We also found that CART neurons in the parvicellular PVH, in the DMH and in the posterior Pe coexpress thyrotropin-releasing hormone (TRH) mRNA. CART neurons in the magnocellular PVH and in the SON coexpress dynorphin (DYN), and CART cell bodies in the LHA and in the posterior Pe coexpress melanin-concentrating hormone (MCH) and glutamic acid decarboxylase (GAD-67) mRNA. In the Arc, a few CART neurons coexpress neurotensin (NT) mRNA. In addition, we examined the distribution of CART immunoreactivity in the human hypothalamus. We found CART cell bodies in the PVH, in the SON, in the LHA, in the Arc (infundibular nucleus) and in the DMH. We also observed CART fibers throughout the hypothalamus, in the bed nucleus of the stria terminalis, and in the amygdala. Our results indicate that leptin directly acts on CART neurons in distinct nuclei of the rat hypothalamus. Furthermore, hypothalamic CART neurons coexpress neuropeptides involved in energy homeostasis, including MCH, TRH, DYN, and NT. The distribution of CART cell bodies and fibers in the human hypothalamos indicates that CART may also play a role in the regulation of energy homeostasis in humans.

Original languageEnglish (US)
Pages (from-to)1-19
Number of pages19
JournalJournal of Comparative Neurology
Volume432
Issue number1
DOIs
StatePublished - Mar 26 2001

Fingerprint

Amphetamine
Cocaine
Hypothalamus
Neurons
Mediodorsal Thalamic Nucleus
Leptin
Messenger RNA
Lateral Hypothalamic Area
Supraoptic Nucleus
Posterior Hypothalamus
Dynorphins
Neurotensin
Arcuate Nucleus of Hypothalamus
Thyrotropin-Releasing Hormone
Neuropeptides
Homeostasis
Leptin Receptors
Septal Nuclei
Peptides
Glutamate Decarboxylase

Keywords

  • Dynorphin
  • Feeding
  • GABA
  • Human hypothalamus
  • Leptin receptor
  • MCH
  • Neurotensin
  • Obesity
  • SOCS-3
  • TRH

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Elias, C. F., Lee, C. E., Kelly, J. F., Ahima, R. S., Kuhar, M., Saper, C. B., & Elmquist, J. K. (2001). Characterization of CART neurons in the rat and human hypothalamus. Journal of Comparative Neurology, 432(1), 1-19. https://doi.org/10.1002/cne.1085

Characterization of CART neurons in the rat and human hypothalamus. / Elias, Carol F.; Lee, Charlotte E.; Kelly, Joseph F.; Ahima, Rexford S.; Kuhar, Michael; Saper, Clifford B.; Elmquist, Joel K.

In: Journal of Comparative Neurology, Vol. 432, No. 1, 26.03.2001, p. 1-19.

Research output: Contribution to journalArticle

Elias, CF, Lee, CE, Kelly, JF, Ahima, RS, Kuhar, M, Saper, CB & Elmquist, JK 2001, 'Characterization of CART neurons in the rat and human hypothalamus', Journal of Comparative Neurology, vol. 432, no. 1, pp. 1-19. https://doi.org/10.1002/cne.1085
Elias CF, Lee CE, Kelly JF, Ahima RS, Kuhar M, Saper CB et al. Characterization of CART neurons in the rat and human hypothalamus. Journal of Comparative Neurology. 2001 Mar 26;432(1):1-19. https://doi.org/10.1002/cne.1085
Elias, Carol F. ; Lee, Charlotte E. ; Kelly, Joseph F. ; Ahima, Rexford S. ; Kuhar, Michael ; Saper, Clifford B. ; Elmquist, Joel K. / Characterization of CART neurons in the rat and human hypothalamus. In: Journal of Comparative Neurology. 2001 ; Vol. 432, No. 1. pp. 1-19.
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