Behavioral, Transcriptomic, and Neuroinflammatory Effects of Sleep Deprivation: Insights From Separate Acute and Chronic Experimental Paradigms.
4 affiliations
- 1Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
- 2Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, China.
- 3The 987th Hospital of Joint Logistics Support force of Chinese People's Liberation Army, BaoJi, China.
- 4State Key Laboratory of Military Stomatology, College of Stomatology, Fourth Military Medical University, Xi'an, China.
Abstract
Background
Depression is a global health burden associated with sleep disruption and inflammation. While acute sleep deprivation (ASD) can alleviate depressive symptoms, chronic sleep deprivation (CSD) is a risk factor for mood disorders. However, the contrasting mechanisms underlying these opposing outcomes remain poorly understood.Methods
We integrated behavioral profiling, multi-region transcriptomics, and multiplex cytokine analysis to separately characterize the effects of ASD in a pain-depression comorbidity model and CSD in normal mice. Adult male C57BL/6J mice (n = 6 per group) were subjected to either a single 6-h total sleep deprivation (ASD) or 6-h daily sleep deprivation for 14 consecutive days (CSD). Behavioral testing included the tail suspension test (TST), open field test (OFT), elevated plus maze (EPM), and sucrose preference test (SPT). Following the interventions, five brain regions-prefrontal cortex (PFC), anterior cingulate cortex (ACC), agranular insular cortex (AI), parietal cortex (PAR), and retrosplenial cortex (RSP)-were dissected. Cytokine levels were quantified using a multiplex panel targeting 15 analytes.Results
Behavioral tests demonstrated that ASD alleviated despair-like behaviors induced by spared nerve injury surgery, whereas CSD resulted in anxiety- and despair-like behaviors. The prefrontal cortex (PFC) exhibited prominent transcriptomic responses to both ASD and CSD, with a substantial number of differentially expressed mRNAs. Transcriptome sequencing confirmed stable differential expression of mRNAs across multiple brain regions. Notable genes linked to depression, including Plin4 and Sult1a1, emerged as potential targets for further research. Ingenuity Pathway Analysis of differentially expressed mRNAs in the PFC indicated that IL-6 and TNF were primarily associated with these changes following ASD. Additionally, inflammatory factors such as BAFF, CHI3L1, IL-4, IL-6R alpha, IL-6, IL-10, TNFRSF1B, IL-12 p70, TWEAK, and osteopontin significantly decreased in the ASD group but increased in the CSD group.Conclusions
This study elucidates that ASD is associated with alleviation of despair-like behaviors and concurrent suppression of multiple inflammatory factors; however, the causal relationship between these observations requires further experimental validation. These findings open new research avenues for identifying potential depression treatment targets. Future research should explore the functional implications of these transcriptomic changes and their relevance for developing novel antidepressant strategies.Significance statement
This study elucidates that ASD is associated with alleviation of despair-like behaviors and concurrent suppression of multiple inflammatory factors; however, the causal relationship between these observations requires further experimental validation. These findings open new research avenues for identifying potential depression treatment targets. Future research should explore the functional implications of these transcriptomic changes and their relevance for developing novel antidepressant strategies.
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BibTeX
@article{cai2026behavioral,
title = {{Behavioral, Transcriptomic, and Neuroinflammatory Effects of Sleep Deprivation: Insights From Separate Acute and Chronic Experimental Paradigms.}},
author = {Guohong Cai and Ming Zhang and Suo Zhao and Yifan Lu and Dingding Yang and Jianhong Duan and Jing Wang and Shengxi Wu and Yan Zhao},
journal = {Brain and behavior},
year = {2026},
month = oct,
doi = {10.1002/brb3.71850},
url = {https://europepmc.org/article/MED/42895810},
note = {CC BY},
}
RIS
TY - JOUR
TI - Behavioral, Transcriptomic, and Neuroinflammatory Effects of Sleep Deprivation: Insights From Separate Acute and Chronic Experimental Paradigms.
AU - Guohong Cai
AU - Ming Zhang
AU - Suo Zhao
AU - Yifan Lu
AU - Dingding Yang
AU - Jianhong Duan
AU - Jing Wang
AU - Shengxi Wu
AU - Yan Zhao
PY - 2026
DA - 2026/10/01
JO - Brain and behavior
DO - 10.1002/brb3.71850
UR - https://europepmc.org/article/MED/42895810
AB - Background Depression is a global health burden associated with sleep disruption and inflammation. While acute sleep deprivation (ASD) can alleviate depressive symptoms, chronic sleep deprivation (CSD) is a risk factor for mood disorders. However, the contrasting mechanisms underlying these opposing outcomes remain poorly understood.Methods We integrated behavioral profiling, multi-region transcriptomics, and multiplex cytokine analysis to separately characterize the effects of ASD in a pain-depression comorbidity model and CSD in normal mice. Adult male C57BL/6J mice (n = 6 per group) were subjected to either a single 6-h total sleep deprivation (ASD) or 6-h daily sleep deprivation for 14 consecutive days (CSD). Behavioral testing included the tail suspension test (TST), open field test (OFT), elevated plus maze (EPM), and sucrose preference test (SPT). Following the interventions, five brain regions-prefrontal cortex (PFC), anterior cingulate cortex (ACC), agranular insular cortex (AI), parietal cortex (PAR), and retrosplenial cortex (RSP)-were dissected. Cytokine levels were quantified using a multiplex panel targeting 15 analytes.Results Behavioral tests demonstrated that ASD alleviated despair-like behaviors induced by spared nerve injury surgery, whereas CSD resulted in anxiety- and despair-like behaviors. The prefrontal cortex (PFC) exhibited prominent transcriptomic responses to both ASD and CSD, with a substantial number of differentially expressed mRNAs. Transcriptome sequencing confirmed stable differential expression of mRNAs across multiple brain regions. Notable genes linked to depression, including Plin4 and Sult1a1, emerged as potential targets for further research. Ingenuity Pathway Analysis of differentially expressed mRNAs in the PFC indicated that IL-6 and TNF were primarily associated with these changes following ASD. Additionally, inflammatory factors such as BAFF, CHI3L1, IL-4, IL-6R alpha, IL-6, IL-10, TNFRSF1B, IL-12 p70, TWEAK, and osteopontin significantly decreased in the ASD group but increased in the CSD group.Conclusions This study elucidates that ASD is associated with alleviation of despair-like behaviors and concurrent suppression of multiple inflammatory factors; however, the causal relationship between these observations requires further experimental validation. These findings open new research avenues for identifying potential depression treatment targets. Future research should explore the functional implications of these transcriptomic changes and their relevance for developing novel antidepressant strategies.Significance statement This study elucidates that ASD is associated with alleviation of despair-like behaviors and concurrent suppression of multiple inflammatory factors; however, the causal relationship between these observations requires further experimental validation. These findings open new research avenues for identifying potential depression treatment targets. Future research should explore the functional implications of these transcriptomic changes and their relevance for developing novel antidepressant strategies.
SN - 2162-3279
ER -