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Maternal deprivation has sexually dimorphic long-term effects on hypothalamic cell-turnover, body weight and circulating hormone levels
Authors:María-Paz Viveros  Ricardo Llorente  Francisca Díaz  Silvana Y Romero-Zerbo  Francisco J Bermudez-Silva  Fernando Rodríguez de Fonseca  Jesús Argente  Julie A Chowen
Institution:aDepartment of Physiology (Animal Physiology II), Faculty of Biology, Universidad Complutense, Madrid, Spain;bDepartment of Endocrinology, Hospital Infantil Universitario Niño Jesús, Department of Pediatrics, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain;cCIBER Fisiopatología de Obesidad y Nutrición, Instituto Carlos III, Madrid, Spain;dLaboratorio de Medicina Regenerativa, Fundación IMABIS, Hospital Carlos Haya, Málaga, Spain
Abstract:Maternal deprivation (MD) has numerous outcomes, including modulation of neuroendocrine functions. We previously reported that circulating leptin levels are reduced and hypothalamic cell-turnover is affected during MD, with some of these effects being sexually dimorphic. As leptin modulates the development of hypothalamic circuits involved in metabolic control, we asked whether MD has long-term consequences on body weight, leptin levels and the expression of neuropeptides involved in metabolism. Rats were separated from their mother for 24 h starting on postnatal day (PND) 9 and sacrificed at PNDs 13, 35 and 75. In both sexes MD reduced body weight, but only until puberty, while leptin levels were unchanged at PND 35 and significantly reduced at PND 75. Adiponectin levels were also reduced at PND 75 in females, while testosterone levels were reduced in males. At PND 13, MD modulated cell-turnover markers in the hypothalamus of males, but not females and increased nestin, a marker of immature neurons, in both sexes, with males having higher levels than females and a significantly greater rise in response to MD. There was no effect of MD on hypothalamic mRNA levels of the leptin receptor or metabolic neuropeptides or the mRNA levels of leptin and adiponectin in adipose tissue. Thus, MD has long-term effects on the levels of circulating hormones that are not correlated with changes in body weight. Furthermore, these endocrine outcomes are different between males and females, which could be due to the fact that MD may have sexually dimorphic effects on hypothalamic development.
Keywords:Neonatal stress  Hypothalamic development  Adipose tissue  Metabolism  Adiponectin  Gonadal steroids
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