Modulation of expression and activity of proteins related to neurogenesis in brain areas involved in emotional and feeding behaviors in the offspring of mice: role of maternal high fat diet pre-and postnatal

Abstract

Recent epidemiological data demonstrate the increased prevalence of Obesity and overweight associated with high intake of High Fat Diet (HFD) in women of childbearing age, pregnant and/or lactating. Currently, 65% of the world population lives in countries where Obesity causes more deaths than malnutrition. Approximately 49% of Brazilians are overweight body. Maternal Obesity induced by HFD increased dramatically over the past 20 years, reaching 42% in African American women and 29% in Caucasian women. Thus, many children are exposed to this "overnutrition" maternal, associated to the consumption of HFD during gestation and lactation periods, phases important for the brain development of the offspring. Therefore, it is essential to investigate possible effects of maternal overnutrition on the development of brain areas related with the feeding and emotional behaviors and energy expenditure in the offspring. However, few studies have investigated the effects of maternal HFD on the brain development of their offspring. Therefore, this research project aims to assess, in the offspring of mice exposed to maternal HFD during periods of pregnancy and lactation, proteins related to neurogenesis in brain areas involved in the control of feeding and emotional behaviors, such as the hippocampus, hypothalamus and Dorsal Raphe nucleus (DR). The protein HES-1 participate in the way signaling for neurogenesis and celular differentiation, regulates the maintenance of stem cells, modulate cell cycle and differentiation, and plays an important role in the maintenance of stem cell/progenitor neural. In addition, other proteins linked neurogenesis also will be studied, such as, NOTCH, MASH and Delta. NOTCH protein is a membrane receptor involved in cell-cell signaling, which can be activated by extracellular signals, such as the protein ligand Delta or Delta-like1 (Dll1). The increased expression of the MASH promotes neuronal differentiation, as it induces the expression of ligands of NOTCH , such as Dll1, which activates protein NOTCH. After the activation of the transmembrane protein NOTCH, the Notch Intracellular Domain (NICD) is released from the transmembrane portion and transferred to the nucleus. NICD will form a complex with Rbpj (binding protein DNA) and Maml (transcriptional co-activator). This complex NICD-Rbpj-Maml induces expression of transcriptional repressors, such as HES-1. The HES-1 then represses gene expression proneural Dll1, leading to inhibition of neuronal differentiation and maintenance of neural progenitor cells. Therefore, we believe that exposure pre and early postnatal of the brains offspring's to maternal HFD, may eventually promote change in this cascade of molecular events that play a fundamental role in neurogenesis. (AU)