{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T22:37:11Z","timestamp":1772663831879,"version":"3.50.1"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,5,11]],"date-time":"2012-05-11T00:00:00Z","timestamp":1336694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Brain and Behavior"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:p><jats:bold>\n            <jats:italic>Myshkin<\/jats:italic> mice heterozygous for an inactivating mutation in the neuron\u2010specific Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>\u2010ATPase <jats:italic>\u03b1<\/jats:italic>3 isoform show behavior analogous to mania, including an abnormal endogenous circadian period. Agrin is a proteoglycan implicated as a regulator of synapses that has been proposed to inhibit activity of Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>\u2010ATPase <jats:italic>\u03b1<\/jats:italic>3. We examined whether the mania\u2010related behavior of <jats:italic>Myshkin<\/jats:italic> mice could be rescued by a reduction in the expression of agrin through genetic knockout. The suppression of agrin reduced hyperambulation and holeboard exploration, restored anxiety\u2010like behavior (or reduced risk\u2010taking behavior), improved prepulse inhibition and shortened the circadian period. Hence, agrin is important for regulating mania\u2010like behavior and circadian rhythms. In <jats:italic>Myshkin<\/jats:italic> mice, the suppression of agrin increased brain Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>\u2010ATPase activity by 11 \u00b1 4%, whereas no effect on Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>\u2010ATPase activity was detected when agrin was suppressed in mice without the <jats:italic>Myshkin<\/jats:italic> mutation. These results introduce agrin as a potential therapeutic target for the treatment of mania and other neurological disorders associated with reduced Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>\u2010ATPase activity and neuronal hyperexcitability.<\/jats:bold><\/jats:p>","DOI":"10.1111\/j.1601-183x.2012.00800.x","type":"journal-article","created":{"date-parts":[[2012,4,20]],"date-time":"2012-04-20T16:06:57Z","timestamp":1334938017000},"page":"436-443","source":"Crossref","is-referenced-by-count":20,"title":["Genetic suppression of agrin reduces mania\u2010like behavior in Na<sup>+<\/sup>, K<sup>+<\/sup>\u2010ATPase <i>\u03b1<\/i>3 mutant mice"],"prefix":"10.1111","volume":"11","author":[{"given":"G. S.","family":"Kirshenbaum","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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