Juvenile Antioxidant Treatment Prevents Adult Deficits in a Developmental Model of Schizophrenia

• DOI: 10.1016/j.neuron.2014.07.028
• Publication Date: 2014-08-14T16:31:43Z
• Authors: Jan-Harry Cabungcal; Danielle S. Counotte; Eastman M. Lewis; Hugo A. Tejeda; Patrick Piantadosi; Cameron Pollock; Gwendolyn G. Calhoon; Elyse M. Sullivan; Echo Presgraves; Jonathan Kil; L. Elliot Hong; Michel Cuenod; Kim Q. Do; Patricio O’Donnell
• Keywords: Neurons; Reflex, Startle; Quinpirole; Neuroscience(all); Excitatory Postsynaptic Potentials; Gene Expression Regulation, Developmental; In Vitro Techniques; Hippocampus; Antioxidants; Drug Administration Schedule; Acetylcysteine; Rats; 3. Good health; Rats, Sprague-Dawley; Disease Models, Animal; Animals, Newborn; Pregnancy; Dopamine Agonists; Excitatory Amino Acid Agonists; Animals; Female; Ibotenic Acid

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.