Neonatal polyI:C treatment in mice results in schizophrenia-like behavioral and neurochemical abnormalities in adulthood

Daisuke Ibi, Taku Nagai, Yuko Kitahara, Hiroyuki Mizoguchi, Hiroyuki Koike, Anna Shiraki, Kazuhiro Takuma, Hiroyuki Kamei, Yukihiro Noda, Atsumi Nitta, Toshitaka Nabeshima, Yukio Yoneda, Kiyofumi Yamada

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)297-305
Number of pages9
JournalNeuroscience Research
Volume64
Issue number3
DOIs
Publication statusPublished - 01-07-2009

Fingerprint

Schizophrenia
Hippocampus
Second Pregnancy Trimester
Glutamic Acid
Sensory Gating
Inbred ICR Mouse
Social Behavior
Virus Diseases
First Pregnancy Trimester
Innate Immunity
Genes
Anxiety
Pregnancy
Control Groups
Messenger RNA
Acids
Brain

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Ibi, Daisuke ; Nagai, Taku ; Kitahara, Yuko ; Mizoguchi, Hiroyuki ; Koike, Hiroyuki ; Shiraki, Anna ; Takuma, Kazuhiro ; Kamei, Hiroyuki ; Noda, Yukihiro ; Nitta, Atsumi ; Nabeshima, Toshitaka ; Yoneda, Yukio ; Yamada, Kiyofumi. / Neonatal polyI:C treatment in mice results in schizophrenia-like behavioral and neurochemical abnormalities in adulthood. In: Neuroscience Research. 2009 ; Vol. 64, No. 3. pp. 297-305.
@article{c474e1554b604a578192de65d40be0dc,
title = "Neonatal polyI:C treatment in mice results in schizophrenia-like behavioral and neurochemical abnormalities in adulthood",
abstract = "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.",
author = "Daisuke Ibi and Taku Nagai and Yuko Kitahara and Hiroyuki Mizoguchi and Hiroyuki Koike and Anna Shiraki and Kazuhiro Takuma and Hiroyuki Kamei and Yukihiro Noda and Atsumi Nitta and Toshitaka Nabeshima and Yukio Yoneda and Kiyofumi Yamada",
year = "2009",
month = "7",
day = "1",
doi = "10.1016/j.neures.2009.03.015",
language = "English",
volume = "64",
pages = "297--305",
journal = "Neuroscience Research",
issn = "0168-0102",
publisher = "Elsevier Ireland Ltd",
number = "3",

}

Ibi, D, Nagai, T, Kitahara, Y, Mizoguchi, H, Koike, H, Shiraki, A, Takuma, K, Kamei, H, Noda, Y, Nitta, A, Nabeshima, T, Yoneda, Y & Yamada, K 2009, 'Neonatal polyI:C treatment in mice results in schizophrenia-like behavioral and neurochemical abnormalities in adulthood', Neuroscience Research, vol. 64, no. 3, pp. 297-305. https://doi.org/10.1016/j.neures.2009.03.015

Neonatal polyI:C treatment in mice results in schizophrenia-like behavioral and neurochemical abnormalities in adulthood. / Ibi, Daisuke; Nagai, Taku; Kitahara, Yuko; Mizoguchi, Hiroyuki; Koike, Hiroyuki; Shiraki, Anna; Takuma, Kazuhiro; Kamei, Hiroyuki; Noda, Yukihiro; Nitta, Atsumi; Nabeshima, Toshitaka; Yoneda, Yukio; Yamada, Kiyofumi.

In: Neuroscience Research, Vol. 64, No. 3, 01.07.2009, p. 297-305.

Research output: Contribution to journalArticle

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

PY - 2009/7/1

Y1 - 2009/7/1

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.

UR - http://www.scopus.com/inward/record.url?scp=65549109489&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65549109489&partnerID=8YFLogxK

U2 - 10.1016/j.neures.2009.03.015

DO - 10.1016/j.neures.2009.03.015

M3 - Article

VL - 64

SP - 297

EP - 305

JO - Neuroscience Research

JF - Neuroscience Research

SN - 0168-0102

IS - 3

ER -