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


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

MOLECULAR PSYCHIATRY, cilt.21, ss.386-393, 2016 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 21 Konu: 3
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1038/mp.2015.61
  • Dergi Adı: MOLECULAR PSYCHIATRY
  • Sayfa Sayıları: ss.386-393

Özet

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.