Daytime dysfunction, including symptoms like sleepiness, poor memory, and reduced responsiveness, is not well researched. It is crucial to develop animal models and study the biological mechanisms involved. We simulated sleep disorders through sleep deprivation, and stressful stimuli were used to establish daytime functional animal models. We used tests like the sodium pentobarbital sleep synergy test and the DSI telemetry system to measure sleep duration and structure. We also used tests like the Morris water maze, open field test, grip test, and baton twirling test to assess mental and physical fatigue. To assess the intrinsic biological mechanisms, we measured sleep–wake-related neurotransmitters and related receptor proteins, circadian rhythm-related proteins and cognition-related proteins in hypothalamus tissue, and oxidative stress, inflammatory factors, S100β, and HPA axis-related indexes in serum. Multi-factor sleep deprivation resulted in the disruption of sleep–wakefulness structure, memory–cognitive function degradation, decreased grip coordination, and other manifestations of decreased energetic and physical strength. The intrinsic biological mechanisms were related to the disturbed expression of sleep–wake, circadian rhythm, memory–cognition-related proteins, as well as the significant elevation of inflammatory factors, oxidative stress, the HPA axis, and other related indicators. Intrinsically related biological mechanisms and reduced sirt1 expression can lead to disruption of circadian rhythms; resulting in disruption of their sleep–wake-related neurotransmitter content and receptor expression. Meanwhile, the reduced expression of sirt1 also resulted in reduced expression of synapse-associated proteins. This study prepared an animal model of daytime dysfunction by means of multi-factor sleep deprivation. With sirt1 as a core target, the relevant biological mechanisms of neurological disorders were modulated.

The aim of this study was to provide a suitable mouse model of radiation-induced delayed reaction and identify potential targets for drug development related to the prevention and treatment of radiation injury. C57BL/6J mice were subjected to singular (109 cGy/min, 5 Gy*1) and fractional (109 cGy/min, 5 Gy*2) total body irradiation. The behavior and activity of mice were assessed 60 days after ionizing radiation (IR) exposure. After that, the pathological changes and mechanism of the mouse brain and femoral tissues were observed by HE, Nissl, Trap staining micro-CT scanning and RNA sequencing (RNA-Seq), and Western blot. The results show that singular or fractional IR exposure led to a decrease in spatial memory ability and activity in mice, and the cognitive and motor functions gradually recovered after singular 5 Gy IR in a time-dependent manner, while the fractional 10 Gy IR group could not recover. The decrease in bone density due to the increase in osteoclast number may be relative to the down-regulation of RUNX2, sclerostin, and beta-catenin. Meanwhile, the brain injury caused by IR exposure is mainly linked to the down-regulation of BNDF and Tau. IR exposure leads to memory impairment, reduced activity, and self-recovery, which are associated with time and dose. The mechanism of cognitive and activity damage was mainly related to oxidative stress and apoptosis induced by DNA damage. The damage caused by fractional 10 Gy TBI is relatively stable and can be used as a stable multi-organ injury model for radiation mechanism research and anti-radiation medicine screening.

Radiation-induced bone injury (RIBI) is a delayed complication of radiotherapy that causes progressive bone loss and impairs skeletal integrity. In this study, we investigated whether phenylethanoid glycosides (PGs) from Cistanche tubulosa (Schenk) Wight could improve RIBI and explored the underlying mechanism. Using a mouse model of delayed radiation-induced bone injury, we found that PGs improved body weight recovery, grip strength, and oxidative stress status after irradiation. Through micro-computed tomography and histological staining to evaluate bone microstructure, it was found that PGs could reduce osteoclast activity after radiation and restore trabecular microstructure, thereby alleviating bone loss caused by radiation. Single-cell RNA sequencing of femoral bone marrow revealed that radiation disrupted the cellular composition of the bone marrow microenvironment and impaired osteogenic programs in bone marrow mesenchymal stem cells. PGs partially restored osteogenic differentiation-related signatures and suppressed adipogenic bias. In osteoblasts, we identified Gremlin-1 (Grem1), a negative regulator of BMP signaling, as a key radiation-responsive gene that was markedly upregulated after irradiation and downregulated by PGs. Western blotting in femoral tissue and MC3T3-E1 cells confirmed that PGs suppressed radiation-induced Grem1 expression. In vitro, PGs promoted alkaline phosphatase activity and mineralization in irradiated osteoblasts. These findings suggest that PGs mitigate RIBI by attenuating oxidative stress, improving bone remodeling, restoring the bone marrow microenvironment, and relieving Grem1-mediated inhibition of osteogenesis. Grem1 may represent a potential therapeutic target for radiation-associated skeletal injury.