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Recent studies have reported that fingolimod, an immunomodulatory drug for treating multiple sclerosis, demonstrates anti\u2010inflammatory and neuroprotective effects in several neurological disease models. This suggests its usefulness for ameliorating cognitive dysfunction in schizophrenia. Herein, we assessed the efficacy profile and mechanism of fingolimod in a rat model of phencyclidine (PCP)\u2010induced schizophrenia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Male Sprague\u2013Dawley rats were treated with PCP for 14\u2009days. The therapeutic effect of fingolimod on cognitive function was assessed using the Morris water maze and fear conditioning tests. Hippocampal neurogenesis and the expression of astrocytes and microglia were evaluated using immunostaining. Cytokine expression was quantified using multiplexed flow cytometry. Brain\u2010derived neurotrophic factor expression and phosphorylation of extracellular signal\u2010regulated kinase were determined using western blot analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Fingolimod attenuated cognitive deficits and restored hippocampal neurogenesis in a dose\u2010dependent manner in PCP\u2010treated rats. Fingolimod treatment exerted anti\u2010inflammatory effects by inhibiting microglial activation and IL\u20106 and IL\u20101\u03b2 pro\u2010inflammatory cytokine expression. The underlying mechanism involves the upregulation of brain\u2010derived neurotrophic factor protein expression and activation of the ERK signalling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>This is the first preclinical assessment of the effects of fingolimod on cognitive function in a model for schizophrenia. Our results suggest the immune system plays an crucial role in cognitive alterations in schizophrenia and highlight the potential of immunomodulatory strategies to improve cognitive deficits in schizophrenia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.15954","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T05:03:57Z","timestamp":1663218237000},"page":"161-173","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Fingolimod ameliorates schizophrenia\u2010like cognitive impairments induced by phencyclidine in male rats"],"prefix":"10.1111","volume":"180","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7820-6880","authenticated-orcid":false,"given":"Xueli","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Affiliated Mental Health Center &amp; Hangzhou Seventh People's Hospital Zhejiang University School of Medicine  Hangzhou 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