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Here the role of the intestinal clock in shaping cognitive function is investigated. It is found that\n                    <jats:italic>Bmal1<\/jats:italic>\n                    \u2010iKO mice (mice with\n                    <jats:italic>Bmal1<\/jats:italic>\n                    [\n                    <jats:italic>Brain and muscle Arnt\u2010like protein 1<\/jats:italic>\n                    ] specifically knocked out in the intestine, a mouse line deficient in intestinal clock function) show a defect in cognitive memory irrespective of the time\u2010of\u2010day.\n                    <jats:italic>Bmal1<\/jats:italic>\n                    \u2010iKO\u2010associated cognitive decline is attributed to impaired adenosine signaling and compromised long\u2010term potentiation (LTP) in the hippocampus. Adenosine signaling promotes LTP via enhancing BDNF expression and inhibiting synapse loss. Furthermore, the impairment in adenosine signaling is accounted for by the reductions in intestinal absorption of and hippocampal level of adenosine but not by a change in adenosine receptors. Consistently, adenosine supplementation rescues cognitive deficits associated with the malfunction of the intestinal clock. Moreover, BMAL1 regulates the expression of ADK (adenosine kinase, a primary enzyme for adenosine clearance) in the small intestine and thus promotes intestinal adenosine absorption through REV\u2010ERB\u03b1 which binds directly to\n                    <jats:italic>Adk<\/jats:italic>\n                    P2 promoter to inhibit its transcription. Together, an unsuspected role of the intestinal clock in controlling cognitive memory is identified, highlighting the intestinal clock as a promising target for the management of cognitive disorders.\n                  <\/jats:p>","DOI":"10.1002\/advs.202504526","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T06:09:30Z","timestamp":1750399770000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Intestinal Clock Promotes Cognitive Memory Through Adenosine Signaling"],"prefix":"10.1002","volume":"12","author":[{"given":"Min","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Molecular Rhythm and Metabolism Guangzhou University of Chinese Medicine  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fugui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Molecular Rhythm and Metabolism Guangzhou 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