title: Role for neonatal D-serine signaling: prevention of physiological and behavioral deficits in adult Pick1 knockout mice.
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.
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Nomura
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: H
authors.initials: H
authors.lastname: Jaaro-Peled
authors.affiliation: Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: E
authors.initials: E
authors.lastname: Lewis
authors.affiliation: Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Nuñez-Abades
authors.affiliation: Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: F
authors.initials: F
authors.lastname: Huppe-Gourgues
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: T
authors.initials: T
authors.lastname: Cash-Padgett
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: F
authors.initials: F
authors.lastname: Emiliani
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Kondo
authors.affiliation: Mental Biology, RIKEN Brain Science Institute, Wako, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Furuya
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Landek-Salgado
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Ayhan
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kamiya
authors.affiliation: Mental Biology, RIKEN Brain Science Institute, Wako, Japan.|Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takumi
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Huganir
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Pletnikov
authors.affiliation: Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: O'Donnell
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sawa
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000367:Age Factors; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005106:Exploratory Behavior / Q000187:drug effects; D005625:Frontal Lobe / Q000473:pathology; D018782:Maze Learning / Q000187:drug effects; D001523:Mental Disorders / Q000188:drug therapy / Q000235:genetics / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000187:drug effects; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics; D065808:Prepulse Inhibition / Q000187:drug effects / Q000235:genetics; D012694:Serine / Q000378:metabolism / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D013550:Swimming / Q000523:psychology; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D009687:Nuclear Proteins; C091822:Prkcabp protein, mouse; D012694:Serine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine