TY - JOUR
T1 - Neonatal polyI:C treatment in mice results in schizophrenia-like behavioral and neurochemical abnormalities in adulthood
AU - Ibi, Daisuke
AU - Nagai, Taku
AU - Kitahara, Yuko
AU - Mizoguchi, Hiroyuki
AU - Koike, Hiroyuki
AU - Shiraki, Anna
AU - Takuma, Kazuhiro
AU - Kamei, Hiroyuki
AU - Noda, Yukihiro
AU - Nitta, Atsumi
AU - Nabeshima, Toshitaka
AU - Yoneda, Yukio
AU - Yamada, Kiyofumi
N1 - Funding Information:
This study was supported in part by a Grant-in-Aid for Scientific Research (No. 19390062) from the Japan Society for the Promotion of Science, Research on Risk of Chemical Substances, Health and Labor Science Grants supported by Ministry of Health, Labour and Welfare, Academic Frontier Project for Private Universities; matching fund subsidy from MEXT, 2007-2011, AstraZeneca Research Grant 2008, and by JST, CREST.
PY - 2009/7
Y1 - 2009/7
N2 - It has been reported that viral infection in the first and second trimesters of pregnancy in humans increases the risk of subsequently developing schizophrenia. To develop a mouse model of immune activation during the early postnatal period, neonatal ICR mice were repeatedly injected with polyriboinosinic-polyribocytidilic acid (polyI:C; an inducer of strong innate immune responses) for 5 days (postnatal day 2-6) which may correspond, in terms of brain development, to the early second trimester in human. Cognitive and emotional behavior as well as the extracellular level of glutamate in the hippocampus were analyzed at the age of 10-12 weeks old. PolyI:C-treated mice showed anxiety-like behavior, impairment of object recognition memory and social behavior, and sensorimotor gating deficits, as compared to the saline-treated control group. Depolarization-evoked glutamate release in the hippocampus was impaired in polyI:C-treated mice compared to saline-treated control mice. Furthermore, to investigate the effect of neonatal immune activation on the expression levels of schizophrenia-related genes, we analyzed mRNA levels in the hippocampus 2 and 24 h after polyI:C treatment. No significant differences or only transient and marginal changes were observed between polyI:C-treated and saline-treated control mice in the expression levels of schizophrenia-related genes in the hippocampus.
AB - It has been reported that viral infection in the first and second trimesters of pregnancy in humans increases the risk of subsequently developing schizophrenia. To develop a mouse model of immune activation during the early postnatal period, neonatal ICR mice were repeatedly injected with polyriboinosinic-polyribocytidilic acid (polyI:C; an inducer of strong innate immune responses) for 5 days (postnatal day 2-6) which may correspond, in terms of brain development, to the early second trimester in human. Cognitive and emotional behavior as well as the extracellular level of glutamate in the hippocampus were analyzed at the age of 10-12 weeks old. PolyI:C-treated mice showed anxiety-like behavior, impairment of object recognition memory and social behavior, and sensorimotor gating deficits, as compared to the saline-treated control group. Depolarization-evoked glutamate release in the hippocampus was impaired in polyI:C-treated mice compared to saline-treated control mice. Furthermore, to investigate the effect of neonatal immune activation on the expression levels of schizophrenia-related genes, we analyzed mRNA levels in the hippocampus 2 and 24 h after polyI:C treatment. No significant differences or only transient and marginal changes were observed between polyI:C-treated and saline-treated control mice in the expression levels of schizophrenia-related genes in the hippocampus.
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U2 - 10.1016/j.neures.2009.03.015
DO - 10.1016/j.neures.2009.03.015
M3 - Article
C2 - 19447299
AN - SCOPUS:65549109489
SN - 0168-0102
VL - 64
SP - 297
EP - 305
JO - Neuroscience Research
JF - Neuroscience Research
IS - 3
ER -