title: Juvenile antioxidant treatment prevents adult deficits in a developmental model of schizophrenia.
abstract: Abnormal development can lead to deficits in adult brain function, a trajectory likely underlying adolescent-onset psychiatric conditions such as schizophrenia. Developmental manipulations yielding adult deficits in rodents provide an opportunity to explore mechanisms involved in a delayed emergence of anomalies driven by developmental alterations. Here we assessed whether oxidative stress during presymptomatic stages causes adult anomalies in rats with a neonatal ventral hippocampal lesion, a developmental rodent model useful for schizophrenia research. Juvenile and adolescent treatment with the antioxidant N-acetyl cysteine prevented the reduction of prefrontal parvalbumin interneuron activity observed in this model, as well as electrophysiological and behavioral deficits relevant to schizophrenia. Adolescent treatment with the glutathione peroxidase mimic ebselen also reversed behavioral deficits in this animal model. These findings suggest that presymptomatic oxidative stress yields abnormal adult brain function in a developmentally compromised brain, and highlight redox modulation as a potential target for early intervention.
authors.affiliation: Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Jan Harry
authors.initials: JH
authors.lastname: Cabungcal
authors.affiliation: Department of Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Danielle S
authors.initials: DS
authors.lastname: Counotte
authors.affiliation: Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Eastman
authors.initials: E
authors.lastname: Lewis
authors.affiliation: Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Tejeda
authors.affiliation: Department of Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Piantadosi
authors.affiliation: Department of Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Cameron
authors.initials: C
authors.lastname: Pollock
authors.affiliation: Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Gwendolyn G
authors.initials: GG
authors.lastname: Calhoon
authors.affiliation: Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Elyse
authors.initials: E
authors.lastname: Sullivan
authors.affiliation: Department of Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Echo
authors.initials: E
authors.lastname: Presgraves
authors.affiliation: Sound Pharmaceuticals, Inc, Research and Development, Seattle, WA, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kil
authors.affiliation: Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.|Maryland Psychiatric Research Center, Baltimore, MD, USA.
authors.forename: L Elliot
authors.initials: LE
authors.lastname: Hong
authors.affiliation: Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Michel
authors.initials: M
authors.lastname: Cuenod
authors.affiliation: Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Kim Q
authors.initials: KQ
authors.lastname: Do
authors.affiliation: Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Patricio
authors.initials: P
authors.lastname: O'Donnell
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000008:administration & dosage*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D004334:Drug Administration Schedule; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development / Q000293:injuries; D007051:Ibotenic Acid / Q000633:toxicity; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D012559:Schizophrenia / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*
chemical_list: D000975:Antioxidants; D018491:Dopamine Agonists; D018690:Excitatory Amino Acid Agonists; D019257:Quinpirole; D007051:Ibotenic Acid; D000111:Acetylcysteine