Fetal programming: on the kidney and neural ontogenesis

Abstract

Subproject 1: Effects of protein restriction in the uterus and exposure to dexamethasone and ncotine in vitro during the nephrogenesis: morphometric and evaluation of gene expression and protein content in stem cells of the cap metanefrogênico. Epidemiological Evidence in diverse populations, as well as experimental results indicates that the nutritional intrauterine conditions "program" the development of hypertension and coronary heart disease in adults. From these results it appears that the gestational, protein deprivation during the active period of nephrogenesis, reduction in the number of clusters at birth. In this way, the predisposition to arterial hypertension can be determined at least in part, by the abnormal development of the kidneys. One of the factors involved in the genesis of fetal programming is the increased exposure of the fetus to the maternal glicocorticoides. However, it is not known if this mechanism is also involved and committed the nephrogenesis process. Recent studies show that the number of stem cells present in the cap mesenchymal (CM), around the end of the bud of the ureter, determines the number of nephron formed. The objective of this subproject is to check the area and the death index and cell proliferation of the cap, the gene expression and the number of positive cells for proteins cell cycle controllers and stem cell marker in CM of the offspring of rats submitted to protein restriction dates, compared to their controls, in different periods of ontogeny. Will still be checked the same parameters in metanephros exposed to dexamethasone (DEX) and nicotine mimicking the high concentration of fetal corticosteroids has demonstrated in gestational protein restriction and smoking. The studies aim to associate the morphometric and gene expression profiles to nephron, as observed in this model. Subproject 2. Analysis of the neural effects of protein restriction in the uterus: morphological and functional and molecular Study during the organogenesis and in adult male rats. Faced with a stressor, the classic answer of "flight or fight" is initiated by activation of the hypothalamic-pituitary-adrenal (HHA), with production of secretory hormone corticotropin-releasing hormone (CRH) and pituitary release of vasopressin and CORTICOTROPIN (ACTH) by the anterior pituitary. This stimulates the adrenal cortex, leading to temporary elevation of circulating corticosteroids. At the same time occurs activation of the autonomic nervous system and increased secretion of catecholamines, which, along with the glucocorticoid and other neuropeptides, contribute to an adequate response to stress. This translates, behaviorally, with an increase in alertness, vigilance and attention. Gradually arise the effects of gene regulation mediated by corticosteroid, through action on mineralo-receptors (MR) and glicocorticoides (GR), expressed in various brain structures. The mineralocorticoid receptors are responsible for the maintenance of excitability and structural integrity of neural networks and are still involved in the process of evaluation of sensory information and your organization. In turn, the glicocorticoides receptors are associated with the end of the response to stress, normalization of homeostasis and storing useful information for future events. These central changes during ontogeny are still poorly understood neural. Thus, taking into account the involvement of the hippocampus in a series of behavioral actions and its modulatory role of response to stress, the present study aims to assess the structural impact of a nutritional stress during pregnancy, relevant to a number of human diseases, not only at the level of the morphology of dendritic tree of pyramidal neurons, but also at the level of synaptic contacts established proximal and distal. (AU)