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

• Published in: Molecular psychiatry Vol. 21; no. 3; pp. 386 - 393
• Main Authors: Nomura, J, Jaaro-Peled, H, 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, A, Takumi, T, Huganir, R, Pletnikov, M, O'Donnell, P, Sawa, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2016; Nature Publishing Group
• Subjects: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - pharmacology; 631/378; 64/110; Action Potentials - drug effects; Action Potentials - genetics; Adults; Age Factors; Alzheimer's disease; Amyotrophic lateral sclerosis; Animal models; Animals; Behavior; Behavioral Sciences; Biological Psychology; Carrier Proteins - genetics; Cortex (frontal); D-Serine; Disease Models, Animal; Dopamine Agonists - pharmacology; Dosage and administration; Excitatory Amino Acid Antagonists - therapeutic use; Exploratory Behavior - drug effects; Forebrain; Frontal Lobe - pathology; Glutamate; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Health aspects; Infants (Newborn); Maze Learning - drug effects; Medicine; Medicine & Public Health; Mental Disorders - drug therapy; Mental Disorders - genetics; Mental Disorders - prevention & control; Methyl aspartate; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity - drug effects; Motor Activity - genetics; N-Methyl-D-aspartic acid receptors; Neonates; Neurons - drug effects; Neurosciences; Neurotransmission; Nuclear Proteins - deficiency; Nuclear Proteins - genetics; original-article; Pharmacotherapy; Physiological aspects; Physiology; Prepulse Inhibition - drug effects; Prepulse Inhibition - genetics; Psychiatry; Rats; Rattus; Receptor mechanisms; Science; Serine - metabolism; Serine - therapeutic use; Signal Transduction - drug effects; Signal Transduction - genetics; Supplements; Swimming - psychology; Synaptic plasticity; Time Factors; Maryland; United States > US; Japan; Baltimore Maryland
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2015.61

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.