Hypothalamic Orexin Projections to the Hippocampal CA1 Region Alleviate Cognitive and Synaptic Plasticity Impairments Induced by Blue Light Exposure.

BACKGROUND AND OBJECTIVES: Exposure to blue light emitted from electronic devices has been shown to impair cognitive performance; however, the mechanisms underlying these deleterious effects remain poorly understood. Orexin neurons in the hypothalamus, which play a key role in modulating cognitive processes and synaptic plasticity, project directly to the hippocampus, a brain region critical for learning and memory. Therefore, our study provides novel insights into the neural mechanisms underlying blue light-related cognitive dysfunction. METHODS AND RESULTS: In this study, we evaluated cognitive impairments in mice subjected to 21 days of blue light exposure using open-field, novel object recognition, and Morris water maze tests. Electrophysiological recordings and Golgi staining revealed that synaptic plasticity was significantly impaired in blue light-exposed mice. The results of biochemical experiments indicated that the expression of Orexin-A, along with the synaptic plasticity-related factors PSD-95 and SYN-1, was downregulated at both the protein and gene levels in the hippocampus of mice following blue light exposure. Furthermore, retrograde tracing combined with immunofluorescence staining showed that hypothalamic orexin neurons projected to the hippocampus, and that CTb-labeled orexin neurons were significantly activated in the hypothalamus (c-FOS(+)) of blue light-exposed mice. Notably, we found that chemogenetic activation of the hypothalamic orexin-hippocampus neural pathway significantly alleviated cognitive functions, accompanied by enhanced expression of Orexin-A, PSD-95, and SYN-1 at both the protein and gene levels. CONCLUSIONS: These findings suggest that the hypothalamic orexin projections to the hippocampal CA1 region alleviate cognitive and synaptic plasticity impairments induced by blue light exposure.