Sex differences in central salt sensing in the human brain

Area of Science:

• Neuroscience
• Physiology
• Endocrinology

Background:

• The organum vasculosum of the lamina terminalis (OVLT) and subfornical organ (SFO) are key brain regions for sensing serum sodium chloride (NaCl) concentration.
• These regions mediate NaCl-induced changes in sympathetic nerve activity, vasopressin (AVP), thirst, and blood pressure (BP).
• Previous human studies show hypernatremia alters SFO and OVLT activity, but sex differences in central NaCl sensing remain unexplored.

Purpose of the Study:

• To investigate sex differences in human central NaCl sensing during acute relative hypernatremia.
• To test the hypothesis that hypernatremia increases functional connectivity between NaCl-sensing regions, with a greater response in men.

Main Methods:

• Thirty-two young adults (17 men, 15 women) underwent resting-state functional magnetic resonance imaging (fMRI).
• fMRI scans were acquired at baseline and during a 30-minute intravenous hypertonic saline infusion.
• Seed-to-seed functional connectivity analysis was performed focusing on the SFO and OVLT.

Main Results:

• Despite similar physiological responses (serum sodium, thirst, BP, AVP) between sexes, a significant time × sex interaction was observed in SFO-OVLT functional connectivity.
• In men, SFO-OVLT functional connectivity increased during the late phase of hypertonic saline infusion (P=0.04).
• In women, SFO-OVLT functional connectivity decreased during the late phase of hypertonic saline infusion (P=0.004).

Conclusions:

• Acute hypernatremia differentially modulates SFO-OVLT functional connectivity between sexes.
• These findings suggest sex-specific regulation of central NaCl sensing pathways.
• Sex differences in the functional coupling of the SFO and OVLT may underlie variations in neurohumoral and cardiovascular responses to hypernatremia.