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Cell. Neurosci."],"abstract":"<jats:p>\n                    Prior work found microglial acid-sensor T-cell death-associated gene 8 (TDAG8) mediates panic-relevant responses to interoceptive stressor CO\n                    <jats:sub>2<\/jats:sub>\n                    inhalation in male mice. Yet panic disorder is more common in women and panic attack symptoms vary in men and women. Here, we investigated sex differences in CO\n                    <jats:sub>2<\/jats:sub>\n                    -evoked behavioral and physiological responses in mice. We also investigated the role of TDAG8 in regulating CO\n                    <jats:sub>2<\/jats:sub>\n                    inhalation-evoked fear-relevant behaviors and hyperventilation, as well as microglial morphology following CO\n                    <jats:sub>2<\/jats:sub>\n                    inhalation in female mice. We found CO\n                    <jats:sub>2<\/jats:sub>\n                    inhalation evoked greater fear-relevant behaviors and hyperventilation in female compared to male mice. Contrary to prior findings in males, we found TDAG8 deletion did not affect fear-relevant defensive responses to CO\n                    <jats:sub>2<\/jats:sub>\n                    inhalation in females. However, TDAG8 deletion significantly attenuated CO\n                    <jats:sub>2<\/jats:sub>\n                    -evoked hyperventilation in females. Previous work in male mice showed CO\n                    <jats:sub>2<\/jats:sub>\n                    inhalation induces morphological indicators of microglial activation within circumventricular organ the subfornical organ (SFO) in a TDAG8-dependent manner. Consistent with males, TDAG8 deletion in females attenuated morphological indicators of microglial activation following CO\n                    <jats:sub>2<\/jats:sub>\n                    inhalation within the SFO, but not within another TDAG8-expressing circumventricular organ, the organ vasculosum of the lamina terminalis (OVLT). This suggests a divergence in the role of TDAG8 in mediating behavioral versus physiological responses to panicogen CO\n                    <jats:sub>2<\/jats:sub>\n                    inhalation, though effects on SFO microglia are consistent. Together these data highlight important sex differences in behavioral and physiological responses to panicogen, CO\n                    <jats:sub>2<\/jats:sub>\n                    inhalation. They also highlight the need to consider phenotypic differences when exploring molecular mechanisms and circuitry driving panic-relevant outcomes in males and females.\n                  <\/jats:p>","DOI":"10.3389\/fncel.2026.1865360","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:46:46Z","timestamp":1786510006000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex differences in responses to panicogen CO2 inhalation and the role of microglial acid-sensor TDAG8 in female mice"],"prefix":"10.3389","volume":"20","author":[{"given":"Shawn","family":"Lam","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Illinois Chicago","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pragnya Sai Priya","family":"Munisetti","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Illinois Chicago","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Ahlbrand","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Systems Physiology, University of Cincinnati","place":["Cincinnati, OH, United States"]},{"name":"Veterans Affairs Medical Center","place":["Cincinnati, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renu","family":"Sah","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Systems Physiology, University of Cincinnati","place":["Cincinnati, OH, United States"]},{"name":"Veterans Affairs Medical Center","place":["Cincinnati, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine M. 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