ORIGINAL RESEARCH article
Front. Sleep
Sec. Sleep, Behavior and Mental Health
Volume 4 - 2025 | doi: 10.3389/frsle.2025.1611192
Sex-and estrous-specific effects of paradoxical sleep deprivation: Neurobehavioral changes and hippocampal neuroinflammation
Provisionally accepted
Laura Olsen*
Krysten A Jones*
Raquel J Moore
Hunter MccubbinsFrances S Curtner
Birendra SharmaCandice N Hatcher-Solis- Air Force Research Laboratory, Dayton, United States
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With millions suffering from sleep disorders in today's modern society, a better understanding of sleep disruption related cognitive outcomes is urgently needed. To that end, a preclinical investigation into the effects of paradoxical sleep deprivation (PPSD) on neurobehavioral outcomes and associated hippocampal neuroinflammation was conducted in male and female rats. Due to epidemiological identification of sex differences in many aspects of sleep disorders, sex and estrous cycle stage factors were investigated. Sprague-Dawley rats underwent 120 h of PPSD using a modified multiple platform 'flower pot' method. At 96 h PPSD, animals were trained on neurobehavioral Novel Object Recognition (NOR) and Passive-Avoidance Task (PAT) paradigms. Prior to NOR/PAT testing at 120 h PSD, Elevated Zero Maze (EZM) assessed anxiolytic-like behavior. PSD impaired PAT performance among males and females. Anxiolytic-like and locomotor behavior was increased and NOR performance impaired in males after PSD. Estrous cycle stage determined by cytological analysis of daily wet smears found females to exhibit estrous-specific differences across all neurobehavioral paradigms, with increased anxiolytic-like behavior and impaired PAT performance only among PSD females in estrus. Immunohistochemical analysis of the hippocampus after 120 h PSD found microgliosis, but not astrogliosis, in the CA1/2 of males and females in estrus. This study contributes to a better understanding of sex-and estrous-specific difference in sleep disruption induced neurobehavioral outcomes and associated hippocampal inflammation. Further research is needed to investigate the molecular mechanisms underlying the interaction between estrous cycle, hippocampal microgliosis, and sleep disruption cognitive outcomes.
Keywords: Sleep Deprivation, Cognition, Estrous Cycle, Microglia, Hippocampus
Received: 13 Apr 2025; Accepted: 08 Aug 2025.
Copyright: © 2025 Olsen, Jones, Moore, Mccubbins, Curtner, Sharma and Hatcher-Solis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Laura Olsen, Air Force Research Laboratory, Dayton, United States
Krysten A Jones, Air Force Research Laboratory, Dayton, United States
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