Research Article
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Neurobehavioral and physiological changes in pregnant rats following REM sleep deprivation model

Year 2026, Volume: 39 Issue: 1, 67 - 72, 28.01.2026
https://doi.org/10.5472/marumj.1873511
https://izlik.org/JA62PD93YH

Abstract

Objective: Sleep is a fundamental physiological process regulated by complex interactions, with interleukins (ILs) playing a key role
in linking the immune system to sleep-wake cycles. Disruptions in this balance, often involving proinflammatory cytokines like IL-1β
and IL-6, contribute to various sleep and neuroinflammatory disorders.
Materials and Methods: This study investigated the effects of REM sleep deprivation (SD) using the multi-platform technique in
pregnant rats for 21 days, followed by behavioral and immunological assays. Rats were subjected to 18 hours of deprivation daily but
allowed 6 hours of recovery sleep.
Results: Behavioral testing showed that SD rats exhibited significantly lower locomotor activity (distance and ambulatory activity)
compared to controls, indicating reduced general motor functions. However, the Elevated Plus Maze revealed no significant difference
in anxiety-like behavior between the groups.
Conclusion: ELISA results demonstrated a statistically significant elevation of both IL-15 and the anti-inflammatory cytokine IL-10
in the SD group. The elevated IL-15 level is interpreted as a marker of potential nerve damage. The increase in IL-10 is suggested to
be a counter-regulatory response to rising pro-inflammatory markers such as IFN-γ, which was also found to be higher, though not
significantly.

References

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  • Irwin MR, Opp MR. Sleep health: Reciprocal regulation of sleep and innate immunity. Neuropsychopharmacology 2017;42:129-55. doi: 10.1038/npp.2016.148
  • Cullen T, Thomas G, Wadley AJ. Sleep deprivation: Cytokine and neuroendocrine effects on perception of effort. Med Sci Sports Exerc 2020;52:909-18. doi: 10.1249/ MSS.000.000.0000002207
  • Gottshall JL, Guedes VA, Pucci JU, et al. Poor sleep quality is linked to elevated extracellular vesicle-associated inflammatory cytokines in warfighters with chronic mild traumatic brain injuries. Front Pharmacol 2021;12:762077. doi: 10.3389/fphar.2021.762077
  • He S, Chen XX, Ge W, et al. Are anti-inflammatory cytokines associated with cognitive impairment in patients with insomnia comorbid with depression? A pilot study. Nat Sci Sleep 2021;13:989-1000. doi: 10.2147/NSS.S312272
  • Irwin MR, Olmstead R, Carroll JE. Sleep disturbance, sleep duration, and inflammation: A systematic review and meta-analysis of cohort studies and experimental sleep deprivation. Biol Psychiatry 2016;80:40-52. doi: 10.1016/j. biopsych.2015.05.014
  • Carroll JE, Carrillo C, Olmstead R, et al. Sleep deprivation and divergent toll-like receptor-4 activation of cellular inflammation in aging. Sleep 2015;38:205-11. doi: 10.5665/ sleep.4398
  • Krysta K, Krzystanek M, Bratek A, Krupka-Matuszczyk I. Sleep and inflammatory markers in different psychiatric disorders. J Neural Transm (Vienna) 2017;124(Suppl 1):179- 86. doi: 10.1007/s00702.015.1492-3
  • Ragnoli B, Pochetti P, Pignatti P, et al. Sleep deprivation, immune suppression and SARS-CoV-2 infection. Int J Environ Res Public Health 2022;19:904. doi: 10.3390/ijerph19020904
  • Saraiva M, O’Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol 2010;10:170-81. doi: 10.1038/nri2711
  • Hurtado-Alvarado G, Pavon L, Castillo-Garcia SA, et al. Sleep loss as a factor to induce cellular and molecular inflammatory variations. Clin Dev Immunol 2013;2013:801341. doi: 10.1155/2013/801341
  • McGeachy MJ, Cua DJ, Gaffen SL. The IL-17 family of cytokines in health and disease. Immunity 2019;50:892-906. doi: 10.1016/j.immuni.2019.03.021
  • Beringer A, Noack M, Miossec P. IL-17 in Chronic inflammation: From discovery to targeting. Trends Mol Med 2016;22:230-41. doi: 10.1016/j.molmed.2016.01.001
  • Machado RB, Suchecki D, Tufik S. Sleep homeostasis in rats assessed by a long-term intermittent paradoxical sleep deprivation protocol. Behav Brain Res 2005;160:356-64. doi: 10.1016/j.bbr.2005.01.001
  • Culpan Y, Ozden L, Gozderesi Y, et al. Effect of methylglyoxal on Parkinson’s disease pathophysiology in the rotenone model. Marmara Med J 2024;37:166-77. doi: 10.5472/ marumj.1480086
  • Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2007;2:322-8. doi: 10.1038/nprot.2007.44
  • Pires GN, Tufik S, Andersen ML. Effects of sleep restriction during pregnancy on postpartum maternal behavior in female rats. Behav Processes 2020;179:104200. doi: 10.1016/j. beproc.2020.104200
  • Dew MA, Hoch CC, Buysse DJ, et al. Healthy older adults’ sleep predicts all-cause mortality at 4 to 19 years of follow-up. Psychosom Med 2003;65:63-73. doi: 10.1097/01. psy.000.003.9756.23250.7c
  • Vgontzas AN, Fernandez-Mendoza J, Liao D, Bixler EO. Insomnia with objective short sleep duration: the most biologically severe phenotype of the disorder. Sleep Med Rev 2013;17:241-54. doi: 10.1016/j.smrv.2012.09.005
  • Irwin MR, Wang M, Campomayor CO, Collado-Hidalgo A, Cole S. Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. Arch Intern Med 2006;166:1756-62. doi: 10.1001/archinte.166.16.1756
  • Shearer WT, Reuben JM, Mullington JM, et al. Soluble TNFalpha receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight. J Allergy Clin Immunol 2001;107:165-70. doi: 10.1067/mai.2001.112270
  • Haack M, Sanchez E, Mullington JM. Elevated inflammatory markers in response to prolonged sleep restriction are associated with increased pain experience in healthy volunteers. Sleep 2007;30:1145-52. doi: 10.1093/sleep/30.9.1145
  • van Leeuwen WM, Lehto M, Karisola P, et al. Sleep restriction increases the risk of developing cardiovascular diseases by augmenting proinflammatory responses through IL- 17 and CRP. PLoS One 2009;4:e4589. doi: 10.1371/journal. pone.0004589
  • Lange T, Dimitrov S, Fehm HL, Westermann J, Born J. Shift of monocyte function toward cellular immunity during sleep. Arch Intern Med 2006;166:1695-700. doi: 10.1001/ archinte.166.16.1695
  • Pan W, Wu X, He Y, et al. Brain interleukin-15 in neuroinflammation and behavior. Neurosci Biobehav Rev 2013;37:184-92. doi: 10.1016/j.neubiorev.2012.11.009
  • Kubota T, Brown RA, Fang J, Krueger JM. Interleukin-15 and interleukin-2 enhance non-REM sleep in rabbits. Am J Physiol Regul Integr Comp Physiol 2001;281:R1004-12. doi: 10.1152/ajpregu.2001.281.3.R1004
  • Huang Z, Ha GK, Petitto JM. IL-15 and IL-15Rα gene deletion:: Effects on T lymphocyte trafficking and the microglial and neuronal responses to facial nerve axotomy. Neurosci Lett 2007;417:160-4. doi: 10.1016/j.neulet.2007.01.086
  • Wu X, He Y, Hsuchou H, Kastin AJ, Rood JC, Pan W. Essential role of interleukin-15 receptor in normal anxiety behavior. Brain Behav Immun 2010;24:1340-6. doi: 10.1016/j. bbi.2010.06.012

Year 2026, Volume: 39 Issue: 1, 67 - 72, 28.01.2026
https://doi.org/10.5472/marumj.1873511
https://izlik.org/JA62PD93YH

Abstract

References

  • Krueger JM, Huang YH, Rector DM, Buysse DJ. Sleep: a synchrony of cell activity-driven small network states. Eur J Neurosci 2013;38:2199-209. doi: 10.1111/ejn.12238
  • Irwin MR, Opp MR. Sleep health: Reciprocal regulation of sleep and innate immunity. Neuropsychopharmacology 2017;42:129-55. doi: 10.1038/npp.2016.148
  • Cullen T, Thomas G, Wadley AJ. Sleep deprivation: Cytokine and neuroendocrine effects on perception of effort. Med Sci Sports Exerc 2020;52:909-18. doi: 10.1249/ MSS.000.000.0000002207
  • Gottshall JL, Guedes VA, Pucci JU, et al. Poor sleep quality is linked to elevated extracellular vesicle-associated inflammatory cytokines in warfighters with chronic mild traumatic brain injuries. Front Pharmacol 2021;12:762077. doi: 10.3389/fphar.2021.762077
  • He S, Chen XX, Ge W, et al. Are anti-inflammatory cytokines associated with cognitive impairment in patients with insomnia comorbid with depression? A pilot study. Nat Sci Sleep 2021;13:989-1000. doi: 10.2147/NSS.S312272
  • Irwin MR, Olmstead R, Carroll JE. Sleep disturbance, sleep duration, and inflammation: A systematic review and meta-analysis of cohort studies and experimental sleep deprivation. Biol Psychiatry 2016;80:40-52. doi: 10.1016/j. biopsych.2015.05.014
  • Carroll JE, Carrillo C, Olmstead R, et al. Sleep deprivation and divergent toll-like receptor-4 activation of cellular inflammation in aging. Sleep 2015;38:205-11. doi: 10.5665/ sleep.4398
  • Krysta K, Krzystanek M, Bratek A, Krupka-Matuszczyk I. Sleep and inflammatory markers in different psychiatric disorders. J Neural Transm (Vienna) 2017;124(Suppl 1):179- 86. doi: 10.1007/s00702.015.1492-3
  • Ragnoli B, Pochetti P, Pignatti P, et al. Sleep deprivation, immune suppression and SARS-CoV-2 infection. Int J Environ Res Public Health 2022;19:904. doi: 10.3390/ijerph19020904
  • Saraiva M, O’Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol 2010;10:170-81. doi: 10.1038/nri2711
  • Hurtado-Alvarado G, Pavon L, Castillo-Garcia SA, et al. Sleep loss as a factor to induce cellular and molecular inflammatory variations. Clin Dev Immunol 2013;2013:801341. doi: 10.1155/2013/801341
  • McGeachy MJ, Cua DJ, Gaffen SL. The IL-17 family of cytokines in health and disease. Immunity 2019;50:892-906. doi: 10.1016/j.immuni.2019.03.021
  • Beringer A, Noack M, Miossec P. IL-17 in Chronic inflammation: From discovery to targeting. Trends Mol Med 2016;22:230-41. doi: 10.1016/j.molmed.2016.01.001
  • Machado RB, Suchecki D, Tufik S. Sleep homeostasis in rats assessed by a long-term intermittent paradoxical sleep deprivation protocol. Behav Brain Res 2005;160:356-64. doi: 10.1016/j.bbr.2005.01.001
  • Culpan Y, Ozden L, Gozderesi Y, et al. Effect of methylglyoxal on Parkinson’s disease pathophysiology in the rotenone model. Marmara Med J 2024;37:166-77. doi: 10.5472/ marumj.1480086
  • Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2007;2:322-8. doi: 10.1038/nprot.2007.44
  • Pires GN, Tufik S, Andersen ML. Effects of sleep restriction during pregnancy on postpartum maternal behavior in female rats. Behav Processes 2020;179:104200. doi: 10.1016/j. beproc.2020.104200
  • Dew MA, Hoch CC, Buysse DJ, et al. Healthy older adults’ sleep predicts all-cause mortality at 4 to 19 years of follow-up. Psychosom Med 2003;65:63-73. doi: 10.1097/01. psy.000.003.9756.23250.7c
  • Vgontzas AN, Fernandez-Mendoza J, Liao D, Bixler EO. Insomnia with objective short sleep duration: the most biologically severe phenotype of the disorder. Sleep Med Rev 2013;17:241-54. doi: 10.1016/j.smrv.2012.09.005
  • Irwin MR, Wang M, Campomayor CO, Collado-Hidalgo A, Cole S. Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. Arch Intern Med 2006;166:1756-62. doi: 10.1001/archinte.166.16.1756
  • Shearer WT, Reuben JM, Mullington JM, et al. Soluble TNFalpha receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight. J Allergy Clin Immunol 2001;107:165-70. doi: 10.1067/mai.2001.112270
  • Haack M, Sanchez E, Mullington JM. Elevated inflammatory markers in response to prolonged sleep restriction are associated with increased pain experience in healthy volunteers. Sleep 2007;30:1145-52. doi: 10.1093/sleep/30.9.1145
  • van Leeuwen WM, Lehto M, Karisola P, et al. Sleep restriction increases the risk of developing cardiovascular diseases by augmenting proinflammatory responses through IL- 17 and CRP. PLoS One 2009;4:e4589. doi: 10.1371/journal. pone.0004589
  • Lange T, Dimitrov S, Fehm HL, Westermann J, Born J. Shift of monocyte function toward cellular immunity during sleep. Arch Intern Med 2006;166:1695-700. doi: 10.1001/ archinte.166.16.1695
  • Pan W, Wu X, He Y, et al. Brain interleukin-15 in neuroinflammation and behavior. Neurosci Biobehav Rev 2013;37:184-92. doi: 10.1016/j.neubiorev.2012.11.009
  • Kubota T, Brown RA, Fang J, Krueger JM. Interleukin-15 and interleukin-2 enhance non-REM sleep in rabbits. Am J Physiol Regul Integr Comp Physiol 2001;281:R1004-12. doi: 10.1152/ajpregu.2001.281.3.R1004
  • Huang Z, Ha GK, Petitto JM. IL-15 and IL-15Rα gene deletion:: Effects on T lymphocyte trafficking and the microglial and neuronal responses to facial nerve axotomy. Neurosci Lett 2007;417:160-4. doi: 10.1016/j.neulet.2007.01.086
  • Wu X, He Y, Hsuchou H, Kastin AJ, Rood JC, Pan W. Essential role of interleukin-15 receptor in normal anxiety behavior. Brain Behav Immun 2010;24:1340-6. doi: 10.1016/j. bbi.2010.06.012
There are 28 citations in total.

Details

Primary Language English
Subjects Surgery (Other)
Journal Section Research Article
Authors

Özlem Kirazlı 0000-0002-4342-8205

Sevdenur Yazi This is me 0000-0003-1325-4205

İrem Peker Eyuboglu 0000-0003-0764-9841

Sercan Doğukan Yıldız This is me 0000-0002-2971-2402

Submission Date October 30, 2025
Acceptance Date December 29, 2025
Publication Date January 28, 2026
DOI https://doi.org/10.5472/marumj.1873511
IZ https://izlik.org/JA62PD93YH
Published in Issue Year 2026 Volume: 39 Issue: 1

Cite

APA Kirazlı, Ö., Yazi, S., Peker Eyuboglu, İ., & Yıldız, S. D. (2026). Neurobehavioral and physiological changes in pregnant rats following REM sleep deprivation model. Marmara Medical Journal, 39(1), 67-72. https://doi.org/10.5472/marumj.1873511
AMA 1.Kirazlı Ö, Yazi S, Peker Eyuboglu İ, Yıldız SD. Neurobehavioral and physiological changes in pregnant rats following REM sleep deprivation model. Marmara Med J. 2026;39(1):67-72. doi:10.5472/marumj.1873511
Chicago Kirazlı, Özlem, Sevdenur Yazi, İrem Peker Eyuboglu, and Sercan Doğukan Yıldız. 2026. “Neurobehavioral and Physiological Changes in Pregnant Rats Following REM Sleep Deprivation Model”. Marmara Medical Journal 39 (1): 67-72. https://doi.org/10.5472/marumj.1873511.
EndNote Kirazlı Ö, Yazi S, Peker Eyuboglu İ, Yıldız SD (January 1, 2026) Neurobehavioral and physiological changes in pregnant rats following REM sleep deprivation model. Marmara Medical Journal 39 1 67–72.
IEEE [1]Ö. Kirazlı, S. Yazi, İ. Peker Eyuboglu, and S. D. Yıldız, “Neurobehavioral and physiological changes in pregnant rats following REM sleep deprivation model”, Marmara Med J, vol. 39, no. 1, pp. 67–72, Jan. 2026, doi: 10.5472/marumj.1873511.
ISNAD Kirazlı, Özlem - Yazi, Sevdenur - Peker Eyuboglu, İrem - Yıldız, Sercan Doğukan. “Neurobehavioral and Physiological Changes in Pregnant Rats Following REM Sleep Deprivation Model”. Marmara Medical Journal 39/1 (January 1, 2026): 67-72. https://doi.org/10.5472/marumj.1873511.
JAMA 1.Kirazlı Ö, Yazi S, Peker Eyuboglu İ, Yıldız SD. Neurobehavioral and physiological changes in pregnant rats following REM sleep deprivation model. Marmara Med J. 2026;39:67–72.
MLA Kirazlı, Özlem, et al. “Neurobehavioral and Physiological Changes in Pregnant Rats Following REM Sleep Deprivation Model”. Marmara Medical Journal, vol. 39, no. 1, Jan. 2026, pp. 67-72, doi:10.5472/marumj.1873511.
Vancouver 1.Özlem Kirazlı, Sevdenur Yazi, İrem Peker Eyuboglu, Sercan Doğukan Yıldız. Neurobehavioral and physiological changes in pregnant rats following REM sleep deprivation model. Marmara Med J. 2026 Jan. 1;39(1):67-72. doi:10.5472/marumj.1873511