DISTRIBUTIONS OF LEPTIN RECEPTOR MESSENGER-RNA ISOFORMS IN THE RAT-BRAIN

Leptin, secreted by white adipocytes, has profound feeding, metabolic, and neuroendocrine effects. Leptin acts on the brain, but the specifi c anatomic sites and pathways responsible for mediating these effects are still unclear. We have systematically examined distributions of mR NA of leptin receptor isoforms in the rat brain by using a probe speci fic for the long form and a probe recognizing all known forms of the l eptin receptor. The mRNA for the long form of the receptor (OB-Rb) loc alized to selected nuclear groups in the rat brain. Within the hypotha lamus, dense hybridization was observed in the arcuate, dorsomedial, v entromedial, and ventral premamillary nuclei. Within the dorsomedial n ucleus, particularly intense hybridization was observed in the caudal regions of the nucleus ventral to the compact formation. Receptors wer e preferentially localized to the dorsomedial division of the ventrome dial nucleus. Hybridization accumulated throughout the arcuate nucleus , extending from the retrochiasmatic region to the posterior periventr icular region. Moderate hybridization was observed in the periventricu lar hypothalamic nucleus, lateral hypothalamic area, medial mammillary nucleus, posterior hypothalamic nucleus, nucleus of the lateral olfac tory tract, and within substantia nigra pars compacta. Several thalami c nuclei were also found to contain dense hybridization. These groups included the mediodorsal, ventral anterior, ventral medial, submedial, ventral posterior, and lateral dorsal thalamic nuclei; Hybridization was also observed in the medial and lateral geniculate nuclei. Intense hybridization was observed in the Purkinje and granular cell layers o f the cerebellum. A probe recognizing all known forms of the leptin re ceptor hybridized to all of these sites within the brain. In addition, intense hybridization was observed in the choroid plexus, meninges, a nd also surrounding blood vessels. These findings indicate that circul ating leptin may act through hypothalamic nuclear groups involved in r egulating feeding, body weight, and neuroendocrine function. The local ization of leptin receptor mRNA in extrahypothalamic sites in the thal amus and cerebellum suggests that leptin may act on specific sensory a nd motor systems. Leptin receptors localized in nonneuronal cells in t he meninges, choroid plexus, and blood vessels may be involved in tran sport of leptin into the brain and in the clearance of leptin from the cerebrospinal fluid. (C) 1998 Wiley-Liss, Inc.