Hypothalamic neurons of postnatally overfed, overweight rats respond differentially to corticotropin-releasing hormones

Adult overweight rats previously subjected to early postnatal overnutrition in small litters are hyperphagic, hyperleptinemic and differ in emotional behaviour from rats of control litters. We proved the hypothesis that neurons of the hypothalamic regulatory system of body weight differentially react to peptides of the corticotropin-releasing factor (CRF) family in these overweight rats. Single unit activity was recorded in brain slices. In controls, CRF and the CRF2 receptor agonist stresscopin-related peptide (SRP) predominantly activated neurons of the dorsomedial part of ventromedial hypothalamic nucleus (VMHDM), but in overweight rats, SRP induced a significant inhibition. Increased neuronal firing to CRF and SRP of the medial parvocellular part of paraventricular hypothalamic nucleus (PaMP) in controls similarly changed to more inhibition in overweight rats. Inhibition of neuronal activity in VMHDM and PaMP can contribute to reduce satiety signals and to decrease energy expenditure in rats. In contrast, medial arcuate (ArcM) neurons of controls were significantly inhibited by SRP, whereas neurons of overweight rats could also be activated. The difference in the expression of these response types was significant. Activation of ArcM neurons known to produce neuropeptide Y can increase food intake. The results are discussed in terms of a trophic action of leptin changing synaptic wiring and the expression of excitatory and inhibitory synapses. The altered responses of hypothalamic neurons in adult small-litter rats may reflect a general mechanism of neurochemical plasticity acquired during the postnatal critical differentiation period, thus leading to permanently altered function of the regulatory system of body weight. (C) 2004 Elsevier Ireland Ltd. All rights reserved.