Dynamic effects of sleep deprivation on emotional behavior, circadian rhythm genes, and inflammatory infiltration in the medial prefrontal cortex

📖 Top 20% JournalJan 29, 2026Frontiers in behavioral neuroscience

Sleep deprivation’s changing effects on emotions, body clock genes, and inflammation in the brain’s decision-making area

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Sleep deprivation (SD) for 7 or 14 days may impair emotional behaviors in mice.

SD leads to increased anxiety-like behaviors, reduced exploration in elevated mazes, and anhedonia, indicated by decreased sucrose preference.
Fear behaviors are also heightened, as shown by prolonged immobility in forced swim and tail suspension tests.
Histological analysis indicates reversible neuronal damage in the medial prefrontal cortex, with complete recovery observed after 21 days of sleep restoration.
Molecular analyses reveal dysregulation of circadian clock genes and activation of the Sirt6/Hmgb1 inflammatory axis, which is associated with proinflammatory cytokine release.
Partial recovery of emotional behaviors occurs after 14 or 21 days of sleep restoration.

AI simplified

BACKGROUND: Sleep, a core circadian rhythm, maintains physiological homeostasis. Its dysfunction links to neuropsychiatric disorders. Clinically, poor sleep impairs positive emotions and enhances negative emotion susceptibility, but the mechanism remains unclear, potentially involving circadian clock genes and neuroinflammatory pathways.

METHODS: Divide the male C57BL/6J mice into the following five groups: Non-sleep deprivation (SD) control (CON), sleep recovery 14-day after SD 7-day (SD7R14), sleep recovery 21-day after SD 7-day (SD7R21), sleep recovery 14-day after SD 14-day (SD14R14), and sleep recovery 21-day after SD 14-day (SD14R21). Behavioral tests evaluated anxiety-like behaviors, fear and andanhedonia. Histological staining observed neuronal morphology in the medial prefrontal cortex (mPFC), and RT-qPCR was employed to measure mRNA levels of circadian clock genes, Silent information regulator 6 (), High mobility group box-1 (), and inflammatory factors. Sirt6Hmgb1

RESULTS: SD induces time-dependent anxiety-like behaviors (reduced exploratory activity in elevated mazes), anhedonia (decreased sucrose preference), and fear behaviors (prolonged immobility in forced swim and tail suspension tests). Histological analysis reveals reversible neuronal damage in the mPFC, with complete recovery observed after 21 days of sleep restitution. Molecular analyses show dysregulation of the muscle aryl-hydrocarbon receptor nuclear translocator-like 1 () and circadian locomotor output cycles kaput () circadian pathway and activation of the Sirt6/Hmgb1 inflammatory axis, leading to proinflammatory cytokine release (), with partial recovery after sleep restoration. Bmal1Clock TNFα, IL1β, COX-2, IL6

CONCLUSION: SD for 7-day or 14-day may impair emotional behaviors by disrupting the RNA expression of clock genes and the Sirt6/Hmgb1 inflammatory axis, while sleep recovery for 14-day or 21-day can partially reverse this impairment.

Full Text

Full text is available at the source.

View full text ↗

Abstract

Full Text

Related papers