{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T19:22:36Z","timestamp":1761765756550},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,1,17]],"date-time":"2014-01-17T00:00:00Z","timestamp":1389916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Recent studies have indicated that dynamic alterations in the structure of postsynaptic density (<jats:styled-content style=\"fixed-case\">PSD<\/jats:styled-content>) are involved in the pathogenesis of many central nervous system disorders, including ischemic stroke. Homer is the newly identified scaffolding protein located at <jats:styled-content style=\"fixed-case\">PSD<\/jats:styled-content> and regulates synaptic function. Homer1a, an immediate early gene, has been shown to be induced by several stimulations, such as glutamate, brain\u2010derived neurotrophic factor, and trauma. However, whether acidosis mediated by acid\u2010sensing ion channels (<jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>s) and hypoxia during cerebral ischemia can change Homer1a expression remains to be determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We investigated that acidosis and hypoxia selectively and rapidly upregulated Homer1a expression, but not Homer1b\/c in cultured cortical neurons. We also found that Homer1a exhibited induction expression in brain cortex of the middle cerebral artery occlusion (<jats:styled-content style=\"fixed-case\">MCAO<\/jats:styled-content>) rats. Additionally, acid\u2010evoked Homer1a <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> induction depended on extracellular signal\u2010regulated kinase1\/2 (<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2) and Akt activity, and <jats:styled-content style=\"fixed-case\">ASIC1a<\/jats:styled-content>\u2010mediated calcium influx whereas hypoxia depended only on <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2 activity. Also, we demonstrated that continuous acidosis and hypoxia resulted in pronounced cell injury and Homer1a knockdown with small interfering <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> aggravated this damage induced by 3\u00a0h acid and hypoxia incubation in neuro\u20102a cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Homer1a might act as an activity\u2010dependent regulator responding to extracellular stimuli during cerebral ischemia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12206","type":"journal-article","created":{"date-parts":[[2014,1,17]],"date-time":"2014-01-17T10:32:47Z","timestamp":1389954767000},"page":"264-274","source":"Crossref","is-referenced-by-count":7,"title":["Acid\u2010sensing Ion Channels Activation and Hypoxia Upregulate Homer1a Expression"],"prefix":"10.1111","volume":"20","author":[{"given":"Jing\u2010Jing","family":"Su","sequence":"first","affiliation":[{"name":"Department of Neurology Shanghai Ninth People's Hospital Shanghai Jiao Tong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Neurology Shanghai Ninth People's Hospital Shanghai Jiao Tong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hou\u2010Guang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology Huashan Hospital Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2010Ping","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology Huashan Hospital Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Neurology Huashan Hospital Fudan University Shanghai 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