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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\u2010related cognitive dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>\n                      In this study, we evaluated cognitive impairments in mice subjected to 21\u2009days of blue light exposure using open\u2010field, novel object recognition, and Morris water maze tests. Electrophysiological recordings and Golgi staining revealed that synaptic plasticity was significantly impaired in blue light\u2010exposed mice. The results of biochemical experiments indicated that the expression of Orexin\u2010A, along with the synaptic plasticity\u2010related factors PSD\u201095 and SYN\u20101, 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\u2010labeled orexin neurons were significantly activated in the hypothalamus (c\u2010FOS\n                      <jats:sup>+<\/jats:sup>\n                      ) of blue light\u2010exposed mice. Notably, we found that chemogenetic activation of the hypothalamic orexin\u2013hippocampus neural pathway significantly alleviated cognitive functions, accompanied by enhanced expression of Orexin\u2010A, PSD\u201095, and SYN\u20101 at both the protein and gene levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that the hypothalamic orexin projections to the hippocampal CA1 region alleviate cognitive and synaptic plasticity impairments induced by blue light exposure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70551","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T06:32:57Z","timestamp":1755498777000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hypothalamic Orexin Projections to the Hippocampal\n                    <scp>CA1<\/scp>\n                    Region Alleviate Cognitive and Synaptic Plasticity Impairments Induced by Blue Light Exposure"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8058-6384","authenticated-orcid":false,"given":"Zhe","family":"Feng","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences Ningxia Medical University  Yinchuan China"},{"name":"Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region Ningxia Medical University  Yinchuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Ningxia Medical University  Yinchuan China"},{"name":"Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region Ningxia Medical University  Yinchuan 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