Electrophysiological Characterization of Sex-Dependent Hypnosis by an Endogenous Neuroactive Steroid Epipregnanolone
Neuroactive steroids (NAS) have long been recognized for their hypnotic and anesthetic properties in both clinical and preclinical settings. While sex differences in NAS sensitivity are acknowledged, the underlying mechanisms remain poorly understood. Here, we examined sex-specific responses to an e...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/15/7/1033 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849732951387930624 |
|---|---|
| author | Tamara Timic Stamenic Ian Coulter Douglas F. Covey Slobodan M. Todorovic |
| author_facet | Tamara Timic Stamenic Ian Coulter Douglas F. Covey Slobodan M. Todorovic |
| author_sort | Tamara Timic Stamenic |
| collection | DOAJ |
| description | Neuroactive steroids (NAS) have long been recognized for their hypnotic and anesthetic properties in both clinical and preclinical settings. While sex differences in NAS sensitivity are acknowledged, the underlying mechanisms remain poorly understood. Here, we examined sex-specific responses to an endogenous NAS epipregnanolone (EpiP) in wild-type mice using behavioral assessment of hypnosis (loss of righting reflex, LORR) and in vivo electrophysiological recordings. Specifically, local field potentials (LFPs) were recorded from the central medial thalamus (CMT) and electroencephalogram (EEG) signals were recorded from the barrel cortex. We found that EpiP-induced LORR exhibited clear sex differences, with females showing increased sensitivity. Spectral power analysis and thalamocortical (TC) and corticocortical (CC) phase synchronization further supported enhanced hypnotic susceptibility in female mice. Our findings reveal characteristic sex-dependent effects of EpiP on the synchronized electrical activity in both thalamus and cortex. These results support renewed exploration of endogenous NAS as clinically relevant anesthetic agents. |
| format | Article |
| id | doaj-art-a1293c9c07f24c24bc6aebebe097acfa |
| institution | DOAJ |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-a1293c9c07f24c24bc6aebebe097acfa2025-08-20T03:08:10ZengMDPI AGBiomolecules2218-273X2025-07-01157103310.3390/biom15071033Electrophysiological Characterization of Sex-Dependent Hypnosis by an Endogenous Neuroactive Steroid EpipregnanoloneTamara Timic Stamenic0Ian Coulter1Douglas F. Covey2Slobodan M. Todorovic3Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Developmental Biology, Washington University School of Medicine, Saint Louis, MO 63101, USADepartment of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USANeuroactive steroids (NAS) have long been recognized for their hypnotic and anesthetic properties in both clinical and preclinical settings. While sex differences in NAS sensitivity are acknowledged, the underlying mechanisms remain poorly understood. Here, we examined sex-specific responses to an endogenous NAS epipregnanolone (EpiP) in wild-type mice using behavioral assessment of hypnosis (loss of righting reflex, LORR) and in vivo electrophysiological recordings. Specifically, local field potentials (LFPs) were recorded from the central medial thalamus (CMT) and electroencephalogram (EEG) signals were recorded from the barrel cortex. We found that EpiP-induced LORR exhibited clear sex differences, with females showing increased sensitivity. Spectral power analysis and thalamocortical (TC) and corticocortical (CC) phase synchronization further supported enhanced hypnotic susceptibility in female mice. Our findings reveal characteristic sex-dependent effects of EpiP on the synchronized electrical activity in both thalamus and cortex. These results support renewed exploration of endogenous NAS as clinically relevant anesthetic agents.https://www.mdpi.com/2218-273X/15/7/1033neuroactive steroidshypnosiselectroencephalogramsex differencesgeneral anesthetics |
| spellingShingle | Tamara Timic Stamenic Ian Coulter Douglas F. Covey Slobodan M. Todorovic Electrophysiological Characterization of Sex-Dependent Hypnosis by an Endogenous Neuroactive Steroid Epipregnanolone Biomolecules neuroactive steroids hypnosis electroencephalogram sex differences general anesthetics |
| title | Electrophysiological Characterization of Sex-Dependent Hypnosis by an Endogenous Neuroactive Steroid Epipregnanolone |
| title_full | Electrophysiological Characterization of Sex-Dependent Hypnosis by an Endogenous Neuroactive Steroid Epipregnanolone |
| title_fullStr | Electrophysiological Characterization of Sex-Dependent Hypnosis by an Endogenous Neuroactive Steroid Epipregnanolone |
| title_full_unstemmed | Electrophysiological Characterization of Sex-Dependent Hypnosis by an Endogenous Neuroactive Steroid Epipregnanolone |
| title_short | Electrophysiological Characterization of Sex-Dependent Hypnosis by an Endogenous Neuroactive Steroid Epipregnanolone |
| title_sort | electrophysiological characterization of sex dependent hypnosis by an endogenous neuroactive steroid epipregnanolone |
| topic | neuroactive steroids hypnosis electroencephalogram sex differences general anesthetics |
| url | https://www.mdpi.com/2218-273X/15/7/1033 |
| work_keys_str_mv | AT tamaratimicstamenic electrophysiologicalcharacterizationofsexdependenthypnosisbyanendogenousneuroactivesteroidepipregnanolone AT iancoulter electrophysiologicalcharacterizationofsexdependenthypnosisbyanendogenousneuroactivesteroidepipregnanolone AT douglasfcovey electrophysiologicalcharacterizationofsexdependenthypnosisbyanendogenousneuroactivesteroidepipregnanolone AT slobodanmtodorovic electrophysiologicalcharacterizationofsexdependenthypnosisbyanendogenousneuroactivesteroidepipregnanolone |