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Neonatal disruption of serine racemase causes schizophrenia-like behavioral abnormalities in adulthood: clinical rescue by d-serine.


ABSTRACT:

Background

D-Serine, an endogenous co-agonist of the N-methyl-D-aspartate (NMDA) receptor, is synthesized from L-serine by serine racemase (SRR). Given the role of D-serine in both neurodevelopment and the pathophysiology of schizophrenia, we examined whether neonatal disruption of D-serine synthesis by SRR inhibition could induce behavioral abnormalities relevant to schizophrenia, in later life.

Methodology/principal findings

Neonatal mice (7-9 days) were injected with vehicle or phenazine methosulfate (Met-Phen: 3 mg/kg/day), an SRR inhibitor. Behavioral evaluations, such as spontaneous locomotion, novel object recognition test (NORT), and prepulse inhibition (PPI) were performed at juvenile (5-6 weeks old) and adult (10-12 weeks old) stages. In addition, we tested the eff

SUBMITTER: Hagiwara H 

PROVIDER: S-EPMC3632541 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature