Choline alleviates cognitive impairment in sleep-deprived young mice via reducing neuroinflammation and altering phospholipidomic profile

Cognitive impairment resulting from insufficient sleep poses a significant public health concern, particularly in children. The effects and mechanisms of choline on cognitive impairment caused by sleep deprivation are unknown. Chronic sleep deprivation is induced in young mice in this study, followed by feeding diet containing 11.36 g/kg choline bitartrate. Choline supplementation significantly improves spatial learning ability. Functional MRI results reveal the hippocampus as a key region affected by sleep deprivation, where choline supplementation notably preserves hippocampal structural integrity and enhanced connectivity. Additionally, choline ameliorates hippocampal pathological injury, reduces blood-brain barrier permeability and serum brain injury biomarkers. Choline also reduces inflammation and oxidative stress biomarkers, and mitigates microglial activation in the hippocampus, which preserves synaptic plasticity. A key finding is the changes of hippocampal phospholipidomic profile along with cognitive function, and a total of 313 phospholipid molecules are identified. Choline increases the levels of total phospholipid and sub-classes (particularly PC), which are strongly correlated with reduced neuroinflammation and oxidative stress biomarkers, as well as improved cognitive outcomes. Furthermore, there are similar findings in some phospholipid molecules such as PC 36:1, PC O-33:0, PC p-38:3, PE 36:3, PE p-42:4 and PS 44:12. These findings highlight that choline alleviates cognitive impairment in sleep deprivation via reducing neuroinflammation and oxidative stress as well as altering phospholipidomic profile. This study suggests that choline could develop into functional food or medicine ingredient to prevent and treat cognitive impairment by sleep disturbances, particularly children and adolescents.