Neuronal Circuits and Neuroendocrine Responses Involved in Dehydration Induced by Water Restriction/Deprivation

Abstract

Body fluid balance is essential for survival. Dehydration caused by water restriction or deprivation induces a loss of intracellular and extracellular fluid (ECF) – decreasing cell and plasma volume – and increases osmolarity. This elevates serum sodium concentrations. Dehydration is also accompanied by thirst and increased salt appetite as well as behavioral responses, such as increased water-seeking and water intake, and ingestion of salt-containing food/fluid in an effort to maintain fluid balance. These changes are mediated in part by the action of the autonomic nervous system and the renin–angiotensin system, but nuclei in the brain also play a crucial role, which is the focus of this review. 1. A variety of brain regions are involved in sensing alterations of body fluid volume and osmolarity. Circumventricular organs (CVOs) including the subfornical organ (SFO), the organum vasculosum laminae terminalis (OVLT), the median preoptic nucleus (MnPO), and the area postrema (AP) contain copious osmoreceptors and are known as the “sensory complex.” In addition, neurons in the nucleus tractus solitarius (NTS) relay peripheral signals to other areas of the brain, and neurons in the lateral parabrachial nucleus (LPB) integrate information from the hypothalamo-neurohypophyseal system (HNS) or the AP/NTS and act to modulate motor behavior. 2. Neurons in the supraoptic nucleus (SON) and hypothalamic paraventricular nucleus (PVN), which receive signals from the intrinsic osmoreceptors and the CVOs as well as NTS, release oxytocin (OT) and arginine vasopressin (AVP) into the general circulation to modulate water retention and natriuresis. These processes are also modulated by classic neurotransmitters such as norepinephrine (NE), glutamate, γ-aminobutyric acid (GABA), nitric oxide (NO), and many other neuropeptide transmitters such as angiotensin II (AngII), corticotrophin-releasing hormone (CRH), apelin, galanin, estrogens (Es), obestatin, orexin, and neuropeptide Y (NPY). 3. In addition to OT, AVP and some other known genes being up- or downregulated, several novel genes are thought to be involved in neuronal responses to dehydration. 4. Glia may also influence water and salt balance via modulation of sodium-level-sensitive sodium channels (Nax), aquaporin-4 water channels (AQP4), and secretion of taurine in CVOs and the HNS. Further investigation of dehydration-induced central neuronal plasticity and remodeling may reveal new drug targets for the treatment of clinical disorders that result in perturbation of water/salt balance.