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


  • Presymptomatic antioxidant treatment prevents loss of parvalbumin in NVHL rats
  • Antioxidant treatment prevents altered prefrontal electrophysiology in NVHL rats
  • Prepulse inhibition deficits are prevented by antioxidants


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.

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