Role for neonatal D-serine signaling: Prevention of physiological and behavioral deficits in adult Pick1 knockout mice

J. Nomura, Hanna Jaaro-Peled, E. Lewis, P. Nuñez-Abades, F. Huppe-Gourgues, T. Cash-Padgett, F. Emiliani, M. A. Kondo, A. Furuya, M. A. Landek-Salgado, Y. Ayhan, Atsushi Kamiya, T. Takumi, Richard L Huganir, Mikhail Pletnikov, P. O'Donnell, Akira Sawa

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)386-393
Number of pages8
JournalMolecular Psychiatry
Volume21
Issue number3
DOIs
StatePublished - Mar 1 2016

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Knockout Mice
Serine
N-Methyl-D-Aspartate Receptors
Neuronal Plasticity
Glutamate Receptors
Brain
Frontal Lobe
Prosencephalon
Synaptic Transmission
Psychiatry
Animal Models
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Role for neonatal D-serine signaling : Prevention of physiological and behavioral deficits in adult Pick1 knockout mice. / Nomura, J.; Jaaro-Peled, Hanna; Lewis, E.; Nuñez-Abades, P.; Huppe-Gourgues, F.; Cash-Padgett, T.; Emiliani, F.; Kondo, M. A.; Furuya, A.; Landek-Salgado, M. A.; Ayhan, Y.; Kamiya, Atsushi; Takumi, T.; Huganir, Richard L; Pletnikov, Mikhail; O'Donnell, P.; Sawa, Akira.

In: Molecular Psychiatry, Vol. 21, No. 3, 01.03.2016, p. 386-393.

Research output: Contribution to journalArticle

Nomura, J, Jaaro-Peled, H, Lewis, E, Nuñez-Abades, P, Huppe-Gourgues, F, Cash-Padgett, T, Emiliani, F, Kondo, MA, Furuya, A, Landek-Salgado, MA, Ayhan, Y, Kamiya, A, Takumi, T, Huganir, RL, Pletnikov, M, O'Donnell, P & Sawa, A 2016, 'Role for neonatal D-serine signaling: Prevention of physiological and behavioral deficits in adult Pick1 knockout mice', Molecular Psychiatry, vol. 21, no. 3, pp. 386-393. https://doi.org/10.1038/mp.2015.61
Nomura, J. ; Jaaro-Peled, Hanna ; Lewis, E. ; Nuñez-Abades, P. ; Huppe-Gourgues, F. ; Cash-Padgett, T. ; Emiliani, F. ; Kondo, M. A. ; Furuya, A. ; Landek-Salgado, M. A. ; Ayhan, Y. ; Kamiya, Atsushi ; Takumi, T. ; Huganir, Richard L ; Pletnikov, Mikhail ; O'Donnell, P. ; Sawa, Akira. / Role for neonatal D-serine signaling : Prevention of physiological and behavioral deficits in adult Pick1 knockout mice. In: Molecular Psychiatry. 2016 ; Vol. 21, No. 3. pp. 386-393.
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