Brain sodium sensing for regulation of thirst, salt appetite, and blood pressure

The brain possesses intricate mechanisms for monitoring sodium (Na) levels in body fluids. During prolonged dehydration, the brain detects variations in body fluids and produces sensations of thirst and aversions to salty tastes. At the core of these processes Na_x , the brain's Na sensor, exists. Specialized neural nuclei, namely the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), which lack the blood-brain barrier, play pivotal roles. Within the glia enveloping the neurons in these regions, Na_x collaborates with Na⁺ /K⁺ -ATPase and glycolytic enzymes to drive glycolysis in response to elevated Na levels. Lactate released from these glia cells activates nearby inhibitory neurons. The SFO hosts distinct types of angiotensin II-sensitive neurons encoding thirst and salt appetite, respectively. During dehydration, Na_x -activated inhibitory neurons suppress salt-appetite neuron's activity, whereas salt deficiency reduces thirst neuron's activity through cholecystokinin. Prolonged dehydration increases the Na sensitivity of Na_x via increased endothelin expression in the SFO. So far, patients with essential hypernatremia have been reported to lose thirst and antidiuretic hormone release due to Na_x -targeting autoantibodies. Inflammation in the SFO underlies the symptoms. Furthermore, Na_x activation in the OVLT, driven by Na retention, stimulates the sympathetic nervous system via acid-sensing ion channels, contributing to a blood pressure elevation.