title: Dietary Intake of Sulforaphane-Rich Broccoli Sprout Extracts during Juvenile and Adolescence Can Prevent Phencyclidine-Induced Cognitive Deficits at Adulthood.
abstract: Oxidative stress and inflammation play a role in cognitive impairment, which is a core symptom of schizophrenia. Furthermore, a hallmark of the pathophysiology of this disease is the dysfunction of cortical inhibitory γ-aminobutyric acid (GABA) neurons expressing parvalbumin (PV), which is also involved in cognitive impairment. Sulforaphane (SFN), an isothiocyanate derived from broccoli, is a potent activator of the transcription factor Nrf2, which plays a central role in the inducible expressions of many cytoprotective genes in response to oxidative stress. Keap1 is a cytoplasmic protein that is essential for the regulation of Nrf2 activity. Here, we found that pretreatment with SFN attenuated cognitive deficits, the increase in 8-oxo-dG-positive cells, and the decrease in PV-positive cells in the medial prefrontal cortex and hippocampus after repeated administration of phencyclidine (PCP). Furthermore, PCP-induced cognitive deficits were improved by the subsequent subchronic administration of SFN. Interestingly, the dietary intake of glucoraphanin (a glucosinolate precursor of SFN) during the juvenile and adolescence prevented the onset of PCP-induced cognitive deficits as well as the increase in 8-oxo-dG-positive cells and the decrease in PV-positive cells in the brain at adulthood. Moreover, the NRF2 gene and the KEAP1 gene had an epistatic effect on cognitive impairment (e.g., working memory and processing speed) in patients with schizophrenia. These findings suggest that SFN may have prophylactic and therapeutic effects on cognitive impairment in schizophrenia. Therefore, the dietary intake of SFN-rich broccoli sprouts during the juvenile and adolescence may prevent the onset of psychosis at adulthood.
authors.affiliation: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Shirai
authors.affiliation: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, Japan; Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ohi
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hidenaga
authors.initials: H
authors.lastname: Yamamori
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yasuda
authors.affiliation: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Ishima
authors.affiliation: Research & Development Division, Kagome Co. Ltd., Tochigi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suganuma
authors.affiliation: Research & Development Division, Kagome Co. Ltd., Tochigi, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ushida
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001937:Brassica / Q000737:chemistry; D002648:Child; D003072:Cognition Disorders / Q000139:chemically induced / Q000178:diet therapy* / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D017879:Isothiocyanates / Q000008:administration & dosage* / Q000737:chemistry; D000072019:Kelch-Like ECH-Associated Protein 1; D051379:Mice; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010622:Phencyclidine / Q000633:toxicity; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D012559:Schizophrenia / Q000178:diet therapy* / Q000473:pathology; D036226:Seedlings / Q000737:chemistry; D013454:Sulfoxides
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D017879:Isothiocyanates; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010936:Plant Extracts; D013454:Sulfoxides; C016766:sulforaphane; D010622:Phencyclidine