Pharmacological and proteomic analyses of neonatal polyI:C-treated adult mice

• Published in: Neuroscience research 2019-10, Vol.147, p.39-47
• Main Authors: Kitagawa, Kanako, Nagai, Taku, Yamada, Kiyofumi
• Format: Article
• Language: English
• Subjects: Aldehyde Dehydrogenase 1 - metabolism; Animal model; Animals; Animals, Newborn; Antipsychotic Agents - pharmacology; Antipsychotic drugs; Behavior; Clozapine - pharmacology; Disease Models, Animal; Exploratory Behavior - drug effects; Female; Haloperidol - pharmacology; Hippocampus - drug effects; Hydrolases - metabolism; Interpersonal Relations; Mice; Microtubule-Associated Proteins - metabolism; Nerve Tissue Proteins; Poly I-C - pharmacology; polyI:C; Pregnancy; Prepulse Inhibition; Proteomics; Recognition, Psychology; Schizophrenia; Schizophrenia - chemically induced; Sensory Gating - drug effects; Viral infection
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2018.10.007

•Neonatal polyI:C treatment caused behavioral abnormalities in adulthood.•Antipsychotics ameliorated behavioral abnormalities in neonatal polyI:C-treated mice.•Proteomic analysis revealed the changes in ALDH1L1 and CRMP5. Perinatal virus infection is an environmental risk factor for neurodevelopmental disorders such as schizophrenia. We previously demonstrated that neonatal treatment with a viral mimetic, polyriboinosinic-polyribocytidilic acid (polyI:C), in mice leads to emotional and cognitive deficits in adolescence. Here, we investigated the effects of antipsychotics on polyI:C-induced behavioral abnormalities. We also performed a proteomic analysis in the hippocampus of polyI:C-treated adult mice using two-dimensional electrophoresis to understand the changes in protein expression following neonatal immune activation. Neonatal mice were subcutaneously injected with polyI:C for 5 days (postnatal day 2–6). At 10 weeks, sensorimotor gating, emotional and cognitive function were analyzed in behavioral tests. Clozapine improved PPI deficit and emotional and cognitive dysfunction in polyI:C-treated mice. However, haloperidol improved only PPI deficit. Proteomic analysis revealed that two candidate proteins were obtained in the hippocampus of polyI:C-treated mice, including aldehyde dehydrogenase family 1 member L1 (ALDH1L1) and collapsin response mediator protein 5 (CRMP5). These data suggest that the neonatal polyI:C-treated mouse model may be useful for evaluating antipsychotic activity of compounds. Moreover, changes in the protein expression of ALDH1L1 and CRMP5 support our previous findings that astrocyte-neuron interaction plays a role in the pathophysiology of neurodevelopmental disorders induced by neonatal immune activation.