{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:38:06Z","timestamp":1792791486133,"version":"4.5.0"},"reference-count":78,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,4,15]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Post\u2010stroke depression (PSD) is a prevalent neuropsychiatric complication of stroke. However, the mechanisms underlying PSD are still unclear. Here, we aimed to investigate the role of HCN1 (hyperpolarization\u2010activated cyclic nucleotide\u2010gated cation channel 1) in the pathogenesis of PSD and its underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">The PSD mice model was established by middle cerebral artery occlusion in\u00a0vivo. Four weeks after middle cerebral artery occlusion, anxiety\u2010 and depression\u2010like behaviors of mice were evaluated by various behavioral tests. HCN channels were downregulated by pharmacological inhibitor or neuron\u2010specific adeno\u2010associated virus. The oxygen\u2013glucose deprivation\/reoxygenation model in SY5Y cells was used to study the pathogenesis of PSD in\u00a0vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Mice exhibited anxiety\u2010 and depression\u2010like behavior 4\u2009weeks after middle cerebral artery occlusion, along with a significant increase in HCN1 protein expression in the ischemic hippocampus. Furthermore, the I\n                      <jats:sub>h<\/jats:sub>\n                      current on neurons in the hippocampus was notably enhanced, whereas neuronal excitability was decreased in PSD mice. Treatment with HCN channel selective inhibitor ZD7288 protected SY5Y cells against oxygen\u2013glucose deprivation\/reoxygenation injury by suppressing K\n                      <jats:sup>+<\/jats:sup>\n                      efflux. Additionally, we observed a significant increase in protein expressions of NLRP3 (nucleotide\u2010binding domain\u2010like receptor protein 3) inflammasome pathway\u2010related molecules in the ischemic hippocampus of PSD mice. Knockdown of HCN1 channels via virus injection into the hippocampus resulted in decreased protein expressions of NLRP3 inflammasome\u2010related molecules and improvement in anxiety\u2010 and depression\u2010like behaviors in PSD mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Downregulation of HCN1 channels has a beneficial effect on PSD by suppressing the NLRP3 inflammasome pathway, thus offering promise as a strategy for preventing and treating PSD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.038263","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T06:07:44Z","timestamp":1744265264000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Downregulation of the HCN1 Channel Alleviates Anxiety\u2010 and Depression\u2010Like Behaviors in Mice With Cerebral Ischemia\u2013Reperfusion Injury by Suppressing the NLRP3 Inflammasome"],"prefix":"10.1161","volume":"14","author":[{"given":"Mei","family":"Zhou","sequence":"first","affiliation":[{"name":"Jianghan University","place":["Wuhan, China"]},{"name":"Institute of Biomedical Sciences, School of Medicine, Jianghan University","place":["Wuhan, China"]},{"name":"Institute of Cerebrovascular Disease, School of Medicine, Jianghan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Tao","sequence":"additional","affiliation":[{"name":"Jianghan University","place":["Wuhan, China"]},{"name":"Institute of Biomedical Sciences, School of Medicine, Jianghan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Jianghan University","place":["Wuhan, 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