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This study investigates the effects of melatonin on hippocampal serine\/threonine kinase signaling in an experimental <jats:styled-content style=\"fixed-case\">ASD<\/jats:styled-content> model. We found that chronic melatonin (1.0 or 5.0\u00a0mg\/kg\/day, 28\u00a0days) treatment significantly rescued valproic acid (<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>, 600\u00a0mg\/kg)\u2010induced decreases in Ca<jats:styled-content style=\"fixed-case\">MKII<\/jats:styled-content> (Thr286), NMDAR1 (Ser896), and <jats:styled-content style=\"fixed-case\">PKA<\/jats:styled-content> (Thr197) phosphorylation in the hippocampus without affecting total protein levels. Compared with control rats, the immunostaining of pyramidal neurons in the hippocampus revealed a decrease in immunolabeling intensity for phospho\u2010Ca<jats:styled-content style=\"fixed-case\">MKII<\/jats:styled-content> (Thr286) in the hippocampus of <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\u2010treated rats, which was ameliorated by chronic melatonin treatment. Consistent with the elevation of Ca<jats:styled-content style=\"fixed-case\">MKII<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PKA<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content> phosphorylation observed in melatonin\u2010treated rat, long\u2010term potentiation (<jats:styled-content style=\"fixed-case\">LTP<\/jats:styled-content>) was enhanced after chronic melatonin (5.0\u00a0mg\/kg) treatment, as reflected by extracellular field potential slopes that increased from 56 to 60\u00a0min (133.4\u00a0\u00b1\u00a03.9% of the baseline, <jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.01 versus <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\u2010treated rats) following high\u2010frequency stimulation (HFS) in hippocampal slices. Accordingly, melatonin treatment also significantly improved social behavioral deficits at postnatal day 50 in <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\u2010treated rats. Taken together, the increased phosphorylation of Ca<jats:styled-content style=\"fixed-case\">MKII<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PKA<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content> signaling might contribute to the beneficial effects of melatonin on autism symptoms.<\/jats:p>","DOI":"10.1111\/jpi.12081","type":"journal-article","created":{"date-parts":[[2013,7,24]],"date-time":"2013-07-24T14:06:40Z","timestamp":1374674800000},"page":"1-11","source":"Crossref","is-referenced-by-count":52,"title":["Melatonin reverses the decreases in hippocampal protein serine\/threonine kinases observed in an animal model of autism"],"prefix":"10.1111","volume":"56","author":[{"given":"Yun","family":"Tian","sequence":"first","affiliation":[{"name":"Institute of Pharmacology Toxicology and Biochemical Pharmaceutics Zhejiang University Hangzhou 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