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Cocaine- and Amphetamine-Regulated Transcript (CART) Is Colocalized with the Orexigenic Neuropeptide Y and Agouti-Related Protein and Absent from the Anorexigenic -Melanocyte-Stimulating Hormone Neurons in the Infundibular Nucleus of the Human Hypothalamus

Department of Endocrine Neurobiology (J.M., G.W., Z.L., C.F.), Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary; Tupper Research Institute and Department of Medicine (R.M.L., C.F.), Division of Endocrinology, Diabetes, Metabolism, and Molecular Medicine, New England Medical Center, Boston, Massachusetts 02111; Department of Neuroscience (R.M.L.), Tufts University School of Medicine, Boston, Massachusetts 02111; Department of Forensic Medicine (É.K.), Semmelweis University, 1085 Budapest, Hungary; and Department of Neuroscience (Z.L.), Faculty of Information Technology, Pázmány Péter Catholic University, 1083 Budapest, Hungary

Address all correspondence and requests for reprints to: Csaba Fekete M.D., Ph.D., Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 43 Szigony Street, 1083 Budapest, Hungary. E-mail: feketecs{at}koki.hu.

Cocaine- and amphetamine-regulated transcript (CART) is a recently discovered anorexigenic peptide. In rodents, CART inhibits food intake and is expressed in the anorexigenic -MSH- but not in the orexigenic neuropeptide Y (NPY)- and agouti-related protein (AGRP)-synthesizing neurons of the arcuate nucleus. To understand whether CART is similarly expressed in feeding-related neuronal groups of the human hypothalamus as observed in rodents, colocalization of CART with -MSH, NPY, AGRP, and melanin-concentrating hormone was studied using double-labeling immunofluorescence and confocal microscopy on human hypothalamic tissues obtained at autopsy. Unlike in rodents, we observed that CART is absent from the perikarya and axons of -MSH-synthesizing neurons, but expressed in approximately one third of NPY/AGRP neurons in the human infundibular nucleus. In the lateral hypothalamus of the humans, colocalization of CART and melanin-concentrating hormone was observed, similar to that described in rodents. The anatomy of CART-containing neurons in the human infundibular nucleus differs markedly from that observed in the rodent brain, raising the question whether the colocalization of CART with orexigenic NPY and AGRP neurons is associated with an orexigenic role of CART in the human brain.