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

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

Blog Article

BackgroundD-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 redken shades eq 07m driftwood neonatal disruption of D-serine synthesis by SRR inhibition could induce behavioral abnormalities relevant to schizophrenia, in later life.Methodology/principal findingsNeonatal 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 effects of D-serine on PPI deficits in adult mice after neonatal Met-Phen exposure.

Finally, we assessed whether D-serine could prevent the onset of schizophrenia-like behavior in these mice.Neonatal Met-Phen treatment reduced D-serine levels in the brain, 24 hours after the final dose.Additionally, this treatment caused behavioral abnormalities relevant to prodromal symptoms in juveniles and to schizophrenia in adults.A single dose of D-serine improved PPI deficits in adult mice.Interestingly, chronic administration of D-serine (900 mg/kg/day from P35 to P70) significantly prevented the onset of PPI deficits after neonatal Met-Phen exposure.

Conclusions/significanceThis study shows that disruption of D-serine synthesis during developmental stages leads to behavioral abnormalities relevant to prodromal symptoms and schizophrenia, in later life.Furthermore, early pharmacological intervention with D-serine may prevent the onset abc material of psychosis in adult.