Subchronic Sleep Fragmentation Induces Endocrine Alterations and Depression-like Behavior in Male Rats.
5 affiliations
- 1Institute of Medical Physiology "Richard Burian", Belgrade University Faculty of Medicine, Visegradska 26/II, 11000 Belgrade, Serbia.
- 2Department for Esophagogastric Disease, Clinic for Digestive Surgery, University Clinical Centre of Serbia, 11000 Belgrade, Serbia.
- 3Department of Biotechnology, Institute of Natural and Applied Sciences, Cukurova University, 01330 Adana, Türkiye.
- 4Institute of Medical and Clinical Biochemistry "Ljubisav Rakić", Belgrade University Faculty of Medicine, 11000 Belgrade, Serbia.
- 5Institute of Pathophysiology "Ljubodrag Buba Mihailovic", Belgrade University Faculty of Medicine, 11000 Belgrade, Serbia.
Abstract
Background
Sleep fragmentation, a hallmark of obstructive sleep apnea (OSA), has been linked to mood disorders through disrupted neuroendocrine regulation. However, the time-dependent development of depression-like behaviors and hormonal changes following recurrent sleep fragmentation remains unclear. This study examined the effects of repeated experimental sleep fragmentation on depression-like behavior and endocrine status in male Wistar rats.Methods
Twenty-four male Wistar rats were randomly assigned to three experimental groups (n = 8 per group): treadmill control (TC; stationary treadmill), activity control (AC; 10-min running/30-min resting cycles), and sleep fragmentation (SF; 30-s running/90-s resting cycles). Treatments were applied daily for 14 consecutive days during the first 6 h of the light phase. Depression-like behavior was assessed via the forced swimming test on days 1, 7, and 14. Body weight was monitored throughout, and serum corticosterone and testosterone were measured at the endpoint. Sleep architecture was inferred from the treadmill protocol rather than directly recorded.Results
SF rats showed progressive increases in immobility and decreases in swimming and climbing over 14 days, reflecting the gradual emergence of depression-like behavior. SF animals also exhibited significantly reduced body-weight gain, elevated corticosterone (p < 0.01), and reduced testosterone (p < 0.001) compared with controls.Conclusions
Subchronic sleep fragmentation induced a progressive depression-like phenotype accompanied by neuroendocrine alterations, suggesting that recurrent sleep interruptions relevant to OSA may contribute to depression-associated endocrine dysregulation. Because sleep architecture was not directly recorded and hormones were measured only at the endpoint, these findings should be interpreted as associative rather than mechanistic.
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BibTeX
@article{grubac2026subchronic,
title = {{Subchronic Sleep Fragmentation Induces Endocrine Alterations and Depression-like Behavior in Male Rats.}},
author = {Zeljko Grubač and Neriman Ezgin and Nikola Šutulović and Djurdja Jerotić and Milena Vesković and Dušan Mladenović and Emilija Đurić and Ana Stojković and Marija Matić and Aleksandra Rašić-Marković and Olivera Stanojlović and Dragan Hrnčić},
journal = {NeuroSci},
year = {2026},
month = oct,
doi = {10.3390/neurosci7050113},
url = {https://europepmc.org/article/MED/42931260},
note = {CC BY},
}
RIS
TY - JOUR
TI - Subchronic Sleep Fragmentation Induces Endocrine Alterations and Depression-like Behavior in Male Rats.
AU - Zeljko Grubač
AU - Neriman Ezgin
AU - Nikola Šutulović
AU - Djurdja Jerotić
AU - Milena Vesković
AU - Dušan Mladenović
AU - Emilija Đurić
AU - Ana Stojković
AU - Marija Matić
AU - Aleksandra Rašić-Marković
AU - Olivera Stanojlović
AU - Dragan Hrnčić
PY - 2026
DA - 2026/10/21
JO - NeuroSci
DO - 10.3390/neurosci7050113
UR - https://europepmc.org/article/MED/42931260
AB - Background Sleep fragmentation, a hallmark of obstructive sleep apnea (OSA), has been linked to mood disorders through disrupted neuroendocrine regulation. However, the time-dependent development of depression-like behaviors and hormonal changes following recurrent sleep fragmentation remains unclear. This study examined the effects of repeated experimental sleep fragmentation on depression-like behavior and endocrine status in male Wistar rats.Methods Twenty-four male Wistar rats were randomly assigned to three experimental groups (n = 8 per group): treadmill control (TC; stationary treadmill), activity control (AC; 10-min running/30-min resting cycles), and sleep fragmentation (SF; 30-s running/90-s resting cycles). Treatments were applied daily for 14 consecutive days during the first 6 h of the light phase. Depression-like behavior was assessed via the forced swimming test on days 1, 7, and 14. Body weight was monitored throughout, and serum corticosterone and testosterone were measured at the endpoint. Sleep architecture was inferred from the treadmill protocol rather than directly recorded.Results SF rats showed progressive increases in immobility and decreases in swimming and climbing over 14 days, reflecting the gradual emergence of depression-like behavior. SF animals also exhibited significantly reduced body-weight gain, elevated corticosterone (p < 0.01), and reduced testosterone (p < 0.001) compared with controls.Conclusions Subchronic sleep fragmentation induced a progressive depression-like phenotype accompanied by neuroendocrine alterations, suggesting that recurrent sleep interruptions relevant to OSA may contribute to depression-associated endocrine dysregulation. Because sleep architecture was not directly recorded and hormones were measured only at the endpoint, these findings should be interpreted as associative rather than mechanistic.
SN - 2673-4087
ER -