The Effects of Sepsis on Osmosensory Neurons Mediating Thirst

Abstract

The ability of osmosensory neurons within the hypothalamus to sense changes in blood osmolality is essential for maintaining hydromineral homeostasis. Typically, an increase in blood osmolality excites the osmosensitive neurons of the organum vasculosum of the lamina terminalis (OVLT), which then stimulate neural pathways to induce thirst sensation. Patient studies show that thirst is depressed in sepsis, a deadly disease defined by the systemic inflammatory response to a severe infection, and that this impairment may be due to a deficit in the osmoregulatory pathway. Using the rat cecal‐ligation and puncture (CLP) sepsis model, we tested the hypothesis that sepsis impairs osmotically‐induced thirst and that this is due to changes in osmosensory OVLT neuron properties. Septic rats did indeed drink significantly less under systemic hypertonic conditions (CLP 4.2 ± 0.58mL; controls 16.4 ± 1.8mL; p < 0.001). Electrophysiological recordings of acute in vitro hypothalamic preparations show that septic OVLT neurons are quiescent due to their hyperpolarized state (CLP −47.9 ± 2.4mV; controls −41.0 ± 2.2mV; p = 0.02). Furthermore, they display an impaired increase in firing rate in response to hypertonicity (CLP 0.1 ± 0.05Hz; controls 0.52 ± 0.18Hz; p < 0.01). These results imply that the CLP rat model mimics the human septic condition, and provide a platform to further our understanding of how central osmoregulation and osmotic thirst are perturbed at a cellular and molecular level in sepsis.