Role for neonatal D-serine signaling: prevention of physiological and behavioral deficits in adult Pickl knockout mice

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Nomura J., Jaaro-Peled H., LEWIS E., NUNEZ-ABADES P., HUPPE-GOURGUES F., Cash-Padgett T., ...More

MOLECULAR PSYCHIATRY, vol.21, no.3, pp.386-393, 2016 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 21 Issue: 3
  • Publication Date: 2016
  • Doi Number: 10.1038/mp.2015.61
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.386-393
  • Hacettepe University Affiliated: Yes


NMDA glutamate receptors have key roles in brain development, function and dysfunction. Regulatory roles of D-serine in NMDA receptor-mediated synaptic plasticity have been reported. Nonetheless, it is unclear whether and how neonatal deficits in NMDA-receptor-mediated neurotransmission affect adult brain functions and behavior. Likewise, the role of D-serine during development remains elusive. Here we report behavioral and electrophysiological deficits associated with the frontal cortex in Pick1 knockout mice, which show D-serine deficits in a neonatal- and forebrain-specific manner. The pathological manifestations observed in adult Pick1 mice are rescued by transient neonatal supplementation of D-serine, but not by a similar treatment in adulthood. These results indicate a role for D-serine in neurodevelopment and provide novel insights on how we interpret data of psychiatric genetics, indicating the involvement of genes associated with D-serine synthesis and degradation, as well as how we consider animal models with neonatal application of NMDA receptor antagonists.