Early developmental expression of leptin receptor gene and [125I]leptin binding in the rat forebrain

German Institute of Human Nutrition, Berlín, Berlin, Germany
Journal of Chemical Neuroanatomy (Impact Factor: 1.5). 05/2007; 33(3):155-63. DOI: 10.1016/j.jchemneu.2007.02.007
Source: PubMed


Leptin, via leptin receptors (Ob-R), regulates appetite and energy balance. Of the six isoforms of the receptor identified, so far, only the long form (Ob-Rb) can fully activate downstream signal transduction pathways. Although the expression and function of leptin receptors is well described in the adult brain, little is known about the ontogeny of leptin receptor system around the time of birth. In this study, the mRNA expression patterns of total leptin receptor, Ob-R, and the long signalling form of the receptor, Ob-Rb, were investigated in the brain of embryonic and newborn rats using in situ hybridisation and [125I]leptin binding. On embryonic day 18 (E18), Ob-R mRNA was detected in the choroid plexus and the ependymal layer of the third ventricle by in situ hybridisation. At E21, Ob-Rb mRNA was first observed in the arcuate and the ventral premammillary hypothalamic nuclei while at P3, receptor expression was also found in the dorsomedial nucleus. Other leptin target areas identified were the trigeminal ganglion, the thalamus and the hippocampus. Using quantitative receptor autoradiography specific [125I]leptin binding sites on the choroid plexus were found to increase with age in contrast to the ependymal layer of the third ventricle where levels decreased with age. Together these findings demonstrate that the leptin receptor system is differentially regulated during late gestation and early postnatal life in the rat.

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Available from: Anne-Sophie Carlo
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    • "Further, circulating levels of leptin surge during the early postnatal period and decline to adult levels during the third postnatal week in rodents (Devaskar et al., 1997; Rayner et al., 1997; Ahima et al., 1998). Intriguingly, although it can reach the brain to activate LepRs during the early postnatal period (Carlo et al., 2007; Pan et al., 2008; Caron et al., 2010), leptin administration at this stage has no effect on food intake nor energy expenditure, in sharp contrast to the adult stage (Campfield et al., 1995; Ahima and Flier, 2000; Proulx et al., 2002). Pointing to a neurotrophic role of leptin during development, neuronal projections from the arcuate nucleus of the hypothalamus (ARH) are severely disturbed in leptin deficient (ob/ob) mice whereas intra-peritoneal delivery of leptin at early but not adult stages is able to rescue this phenotype (Bouret et al., 2004b; Pinto et al., 2004). "
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