title: D-Serine ameliorates neonatal PolyI:C treatment-induced emotional and cognitive impairments in adult mice.
abstract: Polyriboinosinic-polyribocytidilic acid (polyI:C) is a synthetic analog that elicits viral-like immune responses in mammals. We have recently found that polyI:C treatment in neonatal mice induced abnormalities of emotional, cognitive, and sensorimotor gating and dysfunction of glutamatergic neurotransmission in adulthood. In this study, we investigated the effect of the NMDA-receptor co-agonist D-serine on polyI:C-induced behavioral abnormalities in mice. Neonatal ICR mice were repeatedly injected with polyI:C for 5 days from postnatal day 2 to 6. At 10 weeks, sensorimotor gating function was analyzed in the prepulse inhibition (PPI) test. Emotional function was analyzed in open field and social interaction tests. Cognitive function was analyzed by novel object recognition tests. D-Serine dose-dependently improved polyI:C-induced impairment of emotional and cognitive behaviors whereas it had no effect on PPI deficit in adults. The ameliorating effects of D-serine were antagonized by pretreatment with an NMDA-receptor antagonist, MK-801. Although the mRNA level of D-amino acid oxidase (DAAO) was increased in the prefrontal cortex and hippocampus of neonatal polyI:C-treated mice in adulthood, no changes were observed in D-serine content and DAAO enzymatic activity. These results suggest that D-serine ameliorates emotional and cognitive impairments of the polyI:C-treated mice through potentiating NMDA receptor activity.
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Nagai
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yu
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitahara
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000342:Affective Symptoms / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D000831:Animals, Newborn; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D020805:Central Nervous System Viral Diseases / Q000276:immunology / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control*; D003605:D-Amino-Acid Oxidase / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018697:Nootropic Agents / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use; D011897:Random Allocation; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D012694:Serine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use; D013047:Specific Pathogen-Free Organisms
chemical_list: D014151:Anti-Anxiety Agents; D009419:Nerve Tissue Proteins; D018697:Nootropic Agents; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D003605:D-Amino-Acid Oxidase