Altered responses to orexigenic (AGRP, MCH) and anorexigenic (α-MSH, CART) neuropeptides of paraventricular hypothalamic neurons in early postnatally overfed rats

被引:100
作者
Davidowa, H
Li, YZ
Plagemann, A
机构
[1] Humboldt Univ, Fac Med Charite, Johannes Mueller Inst Physiol, D-10117 Berlin, Germany
[2] Humboldt Univ, Fac Med Charite, Inst Expt Endocrinol, D-10098 Berlin, Germany
关键词
body weight regulation; brain slice; malprogramming; obesity; single unit activity;
D O I
10.1046/j.1460-9568.2003.02789.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Food intake and energy expenditure are regulated by neuropeptides in the hypothalamus. While cocaine- and amphetamine-regulated transcript (CART) peptide and melanocortins such as alpha-melanocyte-stimulating hormone (alpha-MSH) are anorexigenic and increase energy expenditure, the endogenous melanocortin receptor antagonist agouti gene-related protein (AGRP), melanin-concentrating hormone (MCH) and neuropeptide Y (NPY) are orexigenic, anabolic peptides. Alterations in the regulatory balance may promote excessive weight gain. The action of these peptides on paraventricular hypothalamic neurons was studied in brain slices of overweight, adult rats previously subjected to early postnatal overfeeding in small litters of only three pups per mother, compared to 12 pups per dam in control litters. CART, melanocortins and NPY significantly excited paraventricular neurons of controls, whereas neurons of small-litter rats were mainly inhibited. Inhibition was dominant following administration of AGRP, MCH and NPY. The altered responses of paraventricular neurons in adult small-litter rats might reflect a general mechanism of neurochemical plasticity and 'malprogramming' of hypothalamic neuropeptidergic systems acquired during the postnatal critical differentiation period, thus leading to permanently altered function of these regulatory systems of body weight.
引用
收藏
页码:613 / 621
页数:9
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