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Sex differences in central salt sensing in the human brain.

Nathan T Romberger1, Joseph M Stock2, Virginia R Nuckols1

  • 1Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware, United States.

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|November 17, 2025
PubMed
Summary

Sex differences exist in brain responses to dehydration. In men, hypernatremia increased functional connectivity between salt-sensing brain regions (SFO and OVLT), while in women, it decreased, suggesting distinct neurohumoral regulation.

Keywords:
NaCl sensingfMRIhypernatremiaosmoreceptorssex differences

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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.