Autonomic Regulation of Cardiovascular Function: Influence of Sex Hormones and Environmental Nano-Contaminants [Doctoral Dissertation Abstract]

With more than a quarter of hypertensive patients resistant to existing antihypertensive therapy, hypertension is a significant public health challenge worldwide.More performant anti-hypertensive drugs are necessary but their development implies a better understanding of molecular mechanisms leading to high blood pressure.It is well described that essential hypertension is correlated with a high sympathetic nerve activity (SNA).Several brain cardiovascular centers (BCCs) located in the brain stem, hypothalamus, and limbic system modulate blood pressure levels by controlling the SNA in both physiological and pathological conditions.The central regulation of cardiovascular function involves complex mechanisms influenced by multiple genetic, hormonal, and environmental factors.The amygdala is a brain area of the limbic system in charge of mediating autonomic responses to stress and regulating negative emotion in the brain of humans, rats, and other mammals.It has neural connections with other BCCs such as nucleus tractus solitarii (NTS), a key region for regulating the set point of blood pressure.Amygdala expresses high estrogen receptor levels and is involved in the control of behavioral and hormonal responses to stress or fear.It is believed that hormonal shift (estrogen deficit) after menopause contributes to women's hypertension and changes in the control of their emotions.Besides, it is reported that the injection of estrogen receptor agonist in medial amygdala prevents stress-induced elevation of blood pressure in ovariectomized rats.However, the involvement of sex hormones in these mechanisms and the neurohormonal mechanisms involved in the changes in blood pressure control are poorly understood.We hypothesized that high estrogen levels contribute to premenopausal characteristics by activating specific genes and pathways of the amygdala involved in the mechanisms regulating basal blood pressure level, motivation, and body weight.We tested the effect of one-month estradiol treatment on the gene expression profile of amygdala in ovariectomized young adult female spontaneously hypertensive rats.Estradiol substitution significantly decreased blood pressure, prevented body weight gain, and increased the voluntary physical activity of ovariectomized rats.In parallel, estradiol treatment downregulated the expression of genes associated with "estrogen signaling pathway," "cholinergic synapse," "dopaminergic synapse," and "long term depression" pathways in the amygdala of ovariectomized rats.These results suggest that the amygdala may be involved in estrogen-dependent regulation of blood pressure, body weight control, and behavior in young adult female spontaneously hypertensive rats and provide a deeper understanding of the underlying mechanisms through which estrogen protects premenopausal women from postmenopausal symptoms.The central nervous system is sensitive to sex hormones and is also vulnerable to nanopollutants.Accumulating evidence shows that nanoplastics (NPs) pollutants may be harmful to the central nervous system to organisms exposed to them on a long term.The potential hazard of the tiniest NPs originates from their capacity to cross biological membranes, be uptaken by cells, and alter their function.According to recent findings, ingested NPs can cross intestinal barriers, travel in the bloodstream, and accumulate in various tissue.Moreover, chronic oral exposure to NPs was shown to induce behavior alteration in rats and reduce locomotor activity in marine species at the early development stage, suggesting that they reach the CNS and alter its functions.NPs are believed to cross blood-brain barriers, and at the cellular level, NPs were shown to trigger neurotoxicity, inflammatory, oxidative stress, and apoptotic response, and be internalized by microglia.However, very little is known about the impact of NPs on neural tissue in vivo, and to our knowledge, virtually no studies are focusing on the effects of NPs on blood-brain barrier-free regions of the central nervous system, such as