title: Early weaning by maternal prolactin inhibition leads to higher neuropeptide Y and astrogliosis in the hypothalamus of the adult rat offspring.
abstract: The suppression of prolactin production with bromocriptine (BRO) in the last 3 d of lactation reduces milk yield (early weaning) and increases the transfer of leptin through the milk, causing hyperleptinaemia in pups. In adulthood, several changes occur in the offspring as a result of metabolic programming, including overweight, higher visceral fat mass, hypothyroidism, hyperglycaemia, insulin resistance, hyperleptinaemia and central leptin resistance. In the present study, we investigated whether overweight rats programmed by early weaning with maternal BRO treatment have hypothalamic alterations in adulthood. We analysed the expression of neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART), pro-opiomelanocortin (POMC) and α-melanocyte-stimulating hormone (α-MSH) by immunohistochemistry in the following hypothalamic nuclei: medial and lateral arcuate nucleus (ARC); paraventricular nucleus (PVN); lateral hypothalamus (LH). Additionally, we sought to determine whether these programmed rats exhibited hypothalamic inflammation as indicated by astrogliosis. NPY immunostaining showed a denser NPY-positive fibre network in the ARC and PVN (+82% in both nuclei) of BRO offspring. Regarding the anorexigenic neuropeptides, no difference was found for CART, POMC and α-MSH. The number of astrocytes was higher in all the nuclei of BRO rats. The fibre density of glial fibrillary acidic protein was also increased in both medial and lateral ARC (6·06-fold increase and 9·13-fold increase, respectively), PVN (5·75-fold increase) and LH (2·68-fold increase) of BRO rats. We suggest that early weaning has a long-term effect on the expression of NPY as a consequence of developmental plasticity, and the presence of astrogliosis indicates hypothalamic inflammation that is closely related to overweight and hyperleptinaemia observed in our model.
authors.affiliation: Laboratório de Fisiologia Endócrina, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro,5° Andar, Av. 28 de Setembro, 87,Rio de Janeiro,RJ20551-031,Brazil.
authors.forename: Viviane
authors.initials: V
authors.lastname: Younes-Rapozo
authors.affiliation: Laboratório de Fisiologia Endócrina, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro,5° Andar, Av. 28 de Setembro, 87,Rio de Janeiro,RJ20551-031,Brazil.
authors.forename: Egberto G
authors.initials: EG
authors.lastname: Moura
authors.affiliation: Laboratório de Neurofisiologia, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro,Rio de Janeiro,Brazil.
authors.forename: Alex C
authors.initials: AC
authors.lastname: Manhães
authors.affiliation: Laboratório de Fisiologia Endócrina, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro,5° Andar, Av. 28 de Setembro, 87,Rio de Janeiro,RJ20551-031,Brazil.
authors.forename: Nayara
authors.initials: N
authors.lastname: Peixoto-Silva
authors.affiliation: Laboratório de Fisiologia Endócrina, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro,5° Andar, Av. 28 de Setembro, 87,Rio de Janeiro,RJ20551-031,Brazil.
authors.forename: Elaine
authors.initials: E
authors.lastname: de Oliveira
authors.affiliation: Laboratório de Fisiologia Endócrina, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro,5° Andar, Av. 28 de Setembro, 87,Rio de Janeiro,RJ20551-031,Brazil.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Lisboa
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000737:chemistry; D005260:Female; D005911:Gliosis / Q000139:chemically induced*; D007031:Hypothalamus / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D007774:Lactation / Q000187:drug effects*; D020738:Leptin / Q000097:blood / Q000378:metabolism; D008297:Male; D008892:Milk / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis; D009478:Neuropeptide Y / Q000032:analysis*; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry; D011247:Pregnancy; D011333:Pro-Opiomelanocortin / Q000032:analysis; D011388:Prolactin / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D014886:Weaning; D000521:alpha-MSH / Q000032:analysis; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D020738:Leptin; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D011388:Prolactin
keywords: Reactive astroglia