{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:45:49Z","timestamp":1790999149341,"version":"4.1.0"},"reference-count":105,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T00:00:00Z","timestamp":1622678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss-National-Science-Foundation","doi-asserted-by":"crossref","award":["320030_122419"],"award-info":[{"award-number":["320030_122419"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National-Center-of-Competence-in-Research"},{"name":"SYNAPSY-The-Synaptic-Bases-of-Mental-Diseases","award":["n\u00b051AU40_125759"],"award-info":[{"award-number":["n\u00b051AU40_125759"]}]},{"name":"Damm-Etienne and Alamaya Foundations"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Research in schizophrenia (SZ) emphasizes the need for new therapeutic approaches based on antioxidant\/anti-inflammatory compounds and psycho-social therapy. A hallmark of SZ is a dysfunction of parvalbumin-expressing fast-spiking interneurons (PVI), which are essential for neuronal synchrony during sensory\/cognitive processing. Oxidative stress and inflammation during early brain development, as observed in SZ, affect PVI maturation. We compared the efficacy of N-acetyl-cysteine (NAC) and\/or environmental enrichment (EE) provided during juvenile and\/or adolescent periods in rescuing PVI impairments induced by an additional oxidative insult during childhood in a transgenic mouse model with gluthation deficit (Gclm KO), relevant for SZ. We tested whether this rescue was promoted by the inhibition of MMP9\/RAGE mechanism, both in the mouse model and in early psychosis (EP) patients, enrolled in a double-blind, randomized, placebo-controlled clinical trial of NAC supplementation for 6 months. We show that a sequential combination of NAC+EE applied after an early-life oxidative insult recovers integrity and function of PVI network in adult Gclm KO, via the inhibition of MMP9\/RAGE. Six-month NAC treatment in EP patients reduces plasma sRAGE in association with increased prefrontal GABA, improvement of cognition and clinical symptoms, suggesting similar neuroprotective mechanisms. The sequential combination of NAC+EE reverses long-lasting effects of an early oxidative insult on PVI\/perineuronal net (PNN) through the inhibition of MMP9\/RAGE mechanism. In analogy, patients vulnerable to early-life insults could benefit from a combined pharmacological and psycho-social therapy.<\/jats:p>","DOI":"10.1093\/schbul\/sbab066","type":"journal-article","created":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T19:11:46Z","timestamp":1620760306000},"page":"1782-1794","source":"Crossref","is-referenced-by-count":40,"title":["Timely N-Acetyl-Cysteine and Environmental Enrichment Rescue Oxidative Stress-Induced Parvalbumin Interneuron Impairments via MMP9\/RAGE Pathway: A Translational Approach for Early Intervention in Psychosis"],"prefix":"10.1093","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4931-9007","authenticated-orcid":false,"given":"Daniella","family":"Dwir","sequence":"first","affiliation":[{"name":"Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Harry","family":"Cabungcal","sequence":"additional","affiliation":[{"name":"Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijing","family":"Xin","sequence":"additional","affiliation":[{"name":"Animal Imaging and Technology Core (AIT), Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fe\u0301de\u0301rale de Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basilio","family":"Giangreco","sequence":"additional","affiliation":[{"name":"Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enea","family":"Parietti","sequence":"additional","affiliation":[{"name":"Center for Psychiatric 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