Children and adolescents globally experience inadequate sleep, which harms their cognitive functions and emotional regulation. The role of circadian clock genes in influencing the antioxidant and anti-inflammatory capabilities has been well-established. Previous studies reported that the impairment of neural activity within the suprachiasmatic nucleus (SCN) can lead to anxiety-like behaviors in mice. Our study was designed to explore the role of BMAL1 expression in SCN, which could be responsible for anxiety-like behaviors induced by chronic sleep restriction (SR) in young mice. Here, 5-week-old male mice were divided into four groups (CONGFP, CONAAV, SRGFP, SRAAV), with chronic sleep restriction applied to the SRGFP group for 4 weeks using an automatic sleep restriction system. Meanwhile, the SRAAV group received AAV injections overexpressing BMAL1 in the SCN before sleep restriction. Anxiety-like behaviors were assessed through the elevated cross-maze and three-box social experiments. In the SRGFP group, there was a significant reduction in the number and duration of mice entering the open arm and the S2 chamber, which was further reduced by BMAL1 overexpression. Mechanistically, BMAL1 compensated for synaptic plasticity damage in the medial prefrontal cortex (mPFC) by upregulating the MAPK-induced inflammatory response, increasing the SOD level, and reducing the MDA level, ultimately restoring BDNF signaling. The study concludes that sleep restriction induces anxiety-like behaviors and impairs synaptic plasticity in the mPFC due to inflammation. Strengthening the molecular clock by BMAL1 overexpression in the SCN alleviated these effects during chronic sleep restriction.
