{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T15:55:17Z","timestamp":1773071717609,"version":"3.50.1"},"reference-count":93,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,20]],"date-time":"2022-08-20T00:00:00Z","timestamp":1660953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology of the Republic of China","award":["105-2628-B-002-004-MY3"],"award-info":[{"award-number":["105-2628-B-002-004-MY3"]}]},{"name":"Ministry of Science and Technology of the Republic of China","award":["108-2320-B-002-066-MY3"],"award-info":[{"award-number":["108-2320-B-002-066-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Symptoms of schizophrenia (SZ) typically emerge during adolescence to young adulthood, which gives a window before full-blown psychosis for early intervention. Strategies for preventing the conversion from the prodromal phase to the psychotic phase are warranted. Heterozygous (Het) Disc1 mutant mice are considered a prodromal model of SZ, suitable for studying psychotic conversion. We evaluated the preventive effect of chronic N-acetylcysteine (NAC) administration, covering the prenatal era to adulthood, on the reaction following the Amph challenge, which mimics the outbreak or conversion of psychosis, in adult Het Disc1 mice. Biochemical and morphological features were examined in the striatum of NAC-treated mice. Chronic NAC treatment normalized the Amph-induced activity in the Het Disc1 mice. Furthermore, the striatal phenotypes of Het Disc1 mice were rescued by NAC including dopamine receptors, the expression of GSK3s, MSN dendritic impairments, and striatal PV density. The current study demonstrated a potent preventive effect of chronic NAC treatment in Disc1 Het mice on the acute Amph test, which mimics the outbreak of psychosis. Our findings not only support the benefit of NAC as a dietary supplement for SZ prodromes, but also advance our knowledge of striatal dopamine receptors, PV neurons, and GSK3 signaling pathways as therapeutic targets for treating or preventing the pathogenesis of mental disorders.<\/jats:p>","DOI":"10.3390\/ijms23169419","type":"journal-article","created":{"date-parts":[[2022,8,21]],"date-time":"2022-08-21T22:23:13Z","timestamp":1661120593000},"page":"9419","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Chronic N-Acetylcysteine Treatment Prevents Amphetamine-Induced Hyperactivity in Heterozygous Disc1 Mutant Mice, a Putative Prodromal Schizophrenia Animal Model"],"prefix":"10.3390","volume":"23","author":[{"given":"Chuan-Ching","family":"Lai","sequence":"first","affiliation":[{"name":"Department of Post-Baccalaureate Veterinary Medicine, Asia University, Taichung 413305, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2676-7379","authenticated-orcid":false,"given":"Rathinasamy","family":"Baskaran","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Medical Engineering, Asia University, Taichung 413305, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Yu","family":"Tsao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei 100233, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Heng","family":"Tuan","sequence":"additional","affiliation":[{"name":"School of Medicine, National Tsing Hua University, Hsinchu 300044, Taiwan"},{"name":"Institute of Systems Neuroscience, National Tsing Hua University, Hsinchu 300044, Taiwan"},{"name":"Department of Medical Science, National Tsing Hua University, Hsinchu 300044, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2864-6324","authenticated-orcid":false,"given":"Pei-Fen","family":"Siow","sequence":"additional","affiliation":[{"name":"Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei 100233, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahalakshmi","family":"Palani","sequence":"additional","affiliation":[{"name":"Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei 100233, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1095-6877","authenticated-orcid":false,"given":"Lukas Jyuhn-Hsiarn","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli 350401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7016-8990","authenticated-orcid":false,"given":"Chih-Min","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 100233, Taiwan"},{"name":"Neurobiology and Cognitive Science Center, National Taiwan University, Taipei 100233, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai-Gwo","family":"Hwu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 100233, Taiwan"},{"name":"Neurobiology and Cognitive Science Center, National Taiwan University, Taipei 100233, Taiwan"},{"name":"Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei 100233, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9108-3654","authenticated-orcid":false,"given":"Li-Jen","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei 100233, Taiwan"},{"name":"Neurobiology and Cognitive Science Center, National Taiwan University, Taipei 100233, Taiwan"},{"name":"Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei 100233, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0896-6273(00)00111-2","article-title":"Catching up on schizophrenia: Natural history and 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