Effects of water deprivation and aging on transcriptome of SON, PVN, ARC and SFO of male and female rats

Abstract

The hypothalamus plays a central role in controlling energy, water and electrolyte homeostasis, reproduction, sexual maturation, circadian rhythms, sleep cycle, and stress. The molecular regulation within the hypothalamic nuclei spans multiple pathways, but of particular importance is the gene expression and its transcriptional and translational regulations. Data analysis from the entire transcriptome commonly results in genes expressed in a specific tissue under different conditions, notably how each gene expression is altered beyond an established threshold. Aging has systemic consequences that can be classified into four processes: body composition, the balance between energy demand and availability, signaling network controlling homeostasis, and neurodegeneration. In adult women, estrogens can influence the hormonal and neural systems that control thirst, fluid intake, sodium appetite, and regulation of renal sodium excretion. However, during menopause, the plasma concentration of these hormones decreases in women and can ultimately modify the hydromineral balance. Furthermore, estradiol modulates neurons on the arcuate nucleus, influencing energy homeostasis. Data from our laboratory have demonstrated the involvement of oxytocin (OT) and atrial natriuretic peptide (ANP) in the fluid and electrolyte balance. Additionally, recent data have shown that OT and ANP have actions on energy homeostasis, influencing the metabolism of adipose tissue. Preliminary data from our laboratory indicate that diet-induced obese animals who were submitted water deprivation displayed a decreased thirst response. Based on that, the current project will investigate the effect of sex, age, treatment with 17²-estradiol as hormonal therapy in aged females on the transcriptome of the paraventricular (PVN), supraoptic (SON), arcuate (ARQ) nucleus, and subfornical organ (SFO) and its relationship with metabolic and hormonal changes in response to dehydration in rats. We will also investigate the effects of OT and ANP on hydroelectrolytic homeostasis on adipose tissue metabolism during the adaptive response to dehydration in control and diet-induced obese animals. (AU)