{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:30:30Z","timestamp":1793345430616,"version":"4.5.0"},"reference-count":64,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Excessive exercise impairs cognition and elevates late\u2010life cognitive risk. However, the underlying mechanisms remain unclear. This study investigates the neural mechanisms through which high\u2010intensity endurance exercise induces cognitive deficits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mice underwent high\u2010loading intensity exercise (HLIE) with a 7\u2010day treadmill procedure (25\u2009m\/min, 90\u2009min\/day). A battery of behavioral tests was conducted to assess cognitive performance, including the Morris Water Maze, Novel Object Recognition, and Y Maze. fMRI and c\u2010Fos activity mapping were employed to identify key brain regions affected by HLIE. Single\u2010nucleus RNA sequencing (snRNA\u2010seq) was conducted to analyze transcriptional changes associated with disrupted neural activity. We used chemogenetic inhibition to identify the role of hippocampal glutamatergic neurons in HLIE\u2010induced cognitive deficits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HLIE caused significant spatial and working memory deficits. The hippocampus (HPC) was the primary brain region affected, exhibiting reduced functional connectivity with the medial prefrontal cortex (mPFC) and disrupted transcriptional profiles linked to neural activity. Further, hippocampal glutamatergic neurons were particularly activated by HLIE, and chemogenetic inhibition prevented cognitive function following HLIE exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HLIE impairs cognition via hippocampal glutamatergic neuronal hyperactivation and downstream HPC\u2010mPFC circuit dysfunction. Our findings identify neuronal calcium dysregulation as a targetable mechanism for preserving cognition in high\u2010intensity exercise paradigms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70928","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T17:16:56Z","timestamp":1781803016000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hippocampal Glutamatergic Hyperactivation Mediates High\u2010Loading Intensity of Exercise\u2010Induced Cognitive Deficits Via\n                    <scp>HPC<\/scp>\n                    \u2010\n                    <scp>mPFC<\/scp>\n                    Circuit Dysfunction"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6145-1281","authenticated-orcid":false,"given":"Qian","family":"Bai","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory of Nutrition and Health, Research Center for Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Institute of Military Preventive Medicine Army Medical University (Third Military Medical University)  Chongqing China"},{"name":"Department of Nutrition, Xinqiao Hospital Army Medical University (Third Military Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Wang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Nutrition and Health, Research Center for Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Institute of Military Preventive Medicine Army Medical University (Third Military Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hedong","family":"Lang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Nutrition and Health, Research Center for Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, 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