TY - JOUR
T1 - Pharmacological and proteomic analyses of neonatal polyI:C-treated adult mice
AU - Kitagawa, Kanako
AU - Nagai, Taku
AU - Yamada, Kiyofumi
N1 - Funding Information:
We wish to acknowledge Division for Medical Research Engineering and Division of Experimental Animals at Nagoya University Graduate School of Medicine for technical assistance. This work was supported by the following funding sources: KAKENHI Grant Numbers JP17H04031, JP17H02220, JP16K15201, JP15H01284, 25116515, and 17K19483 from JSPS; the JP18dm0107087 and JP18mk0101076 from AMED; a Grant for Biomedical Research from SRF; the Pharmacological Research Foundation, Tokyo; The Uehara Memorial Foundation.
Funding Information:
We wish to acknowledge Division for Medical Research Engineering and Division of Experimental Animals at Nagoya University Graduate School of Medicine for technical assistance. This work was supported by the following funding sources: KAKENHI Grant Numbers JP17H04031 , JP17H02220 , JP16K15201 , JP15H01284 , 25116515 , and 17K19483 from JSPS ; the JP18dm0107087 and JP18mk0101076 from AMED ; a Grant for Biomedical Research from SRF ; the Pharmacological Research Foundation, Tokyo ; The Uehara Memorial Foundation .
PY - 2019/10
Y1 - 2019/10
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neures.2018.10.007
DO - 10.1016/j.neures.2018.10.007
M3 - Article
C2 - 31446906
AN - SCOPUS:85055710696
VL - 147
SP - 39
EP - 47
JO - Neuroscience Research
JF - Neuroscience Research
SN - 0168-0102
ER -