Combined effect of neonatal immune activation and mutant DISC1 on phenotypic changes in adulthood

Daisuke Ibi, Taku Nagai, Hiroyuki Koike, Yuko Kitahara, Hiroyuki Mizoguchi, Minae Niwa, Hanna Jaaro-Peled, Atsumi Nitta, Yukio Yoneda, Toshitaka Nabeshima, Akira Sawa, Kiyofumi Yamada

Research output: Contribution to journalArticle

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Abstract

Gene-environment interaction may play a role in the etiology of schizophrenia. Transgenic mice expressing dominant-negative DISC1 (DN-DISC1 mice) show some histological and behavioral endophenotypes relevant to schizophrenia. Viral infection during neurodevelopment provides a major environmental risk for schizophrenia. Neonatal injection of polyriboinosinic-polyribocytidylic acid (polyI:C), which mimics innate immune responses elicited by viral infection, leads to schizophrenia-like behavioral alteration in mice after puberty. To study how gene-environmental interaction during neurodevelopment results in phenotypic changes in adulthood, we treated DN-DISC1 mice or wild-type littermates with injection of polyI:C during the neonatal stage, according to the published method, respectively, and the behavioral and histological phenotypes were examined in adulthood. We demonstrated that neonatal polyI:C treatment in DN-DISC1 mice resulted in the deficits of short-term, object recognition, and hippocampus-dependent fear memories after puberty, although polyI:C treatment by itself had smaller influences on wild-type mice. Furthermore, polyI:C-treated DN-DISC1 mice exhibited signs of impairment of social recognition and interaction, and augmented susceptibility to MK-801-induced hyperactivity as compared with vehicle-treated wild-type mice. Of most importance, additive effects of polyI:C and DN-DISC1 were observed by a marked decrease in parvalbumin-positive interneurons in the medial prefrontal cortex. These results suggest that combined effect of neonatal polyI:C treatment and DN-DISC1 affects some behavioral and histological phenotypes in adulthood.

Original languageEnglish
Pages (from-to)32-37
Number of pages6
JournalBehavioural Brain Research
Volume206
Issue number1
DOIs
Publication statusPublished - 05-01-2010

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Acids
Schizophrenia
Virus Diseases
Puberty
Endophenotypes
Phenotype
Parvalbumins
Gene-Environment Interaction
Injections
Dizocilpine Maleate
Interneurons
Interpersonal Relations
Prefrontal Cortex
Innate Immunity
Transgenic Mice
Fear
Hippocampus
Therapeutics
Genes
Recognition (Psychology)

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

Cite this

Ibi, D., Nagai, T., Koike, H., Kitahara, Y., Mizoguchi, H., Niwa, M., ... Yamada, K. (2010). Combined effect of neonatal immune activation and mutant DISC1 on phenotypic changes in adulthood. Behavioural Brain Research, 206(1), 32-37. https://doi.org/10.1016/j.bbr.2009.08.027
Ibi, Daisuke ; Nagai, Taku ; Koike, Hiroyuki ; Kitahara, Yuko ; Mizoguchi, Hiroyuki ; Niwa, Minae ; Jaaro-Peled, Hanna ; Nitta, Atsumi ; Yoneda, Yukio ; Nabeshima, Toshitaka ; Sawa, Akira ; Yamada, Kiyofumi. / Combined effect of neonatal immune activation and mutant DISC1 on phenotypic changes in adulthood. In: Behavioural Brain Research. 2010 ; Vol. 206, No. 1. pp. 32-37.
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Ibi, D, Nagai, T, Koike, H, Kitahara, Y, Mizoguchi, H, Niwa, M, Jaaro-Peled, H, Nitta, A, Yoneda, Y, Nabeshima, T, Sawa, A & Yamada, K 2010, 'Combined effect of neonatal immune activation and mutant DISC1 on phenotypic changes in adulthood', Behavioural Brain Research, vol. 206, no. 1, pp. 32-37. https://doi.org/10.1016/j.bbr.2009.08.027

Combined effect of neonatal immune activation and mutant DISC1 on phenotypic changes in adulthood. / Ibi, Daisuke; Nagai, Taku; Koike, Hiroyuki; Kitahara, Yuko; Mizoguchi, Hiroyuki; Niwa, Minae; Jaaro-Peled, Hanna; Nitta, Atsumi; Yoneda, Yukio; Nabeshima, Toshitaka; Sawa, Akira; Yamada, Kiyofumi.

In: Behavioural Brain Research, Vol. 206, No. 1, 05.01.2010, p. 32-37.

Research output: Contribution to journalArticle

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T1 - Combined effect of neonatal immune activation and mutant DISC1 on phenotypic changes in adulthood

AU - Ibi, Daisuke

AU - Nagai, Taku

AU - Koike, Hiroyuki

AU - Kitahara, Yuko

AU - Mizoguchi, Hiroyuki

AU - Niwa, Minae

AU - Jaaro-Peled, Hanna

AU - Nitta, Atsumi

AU - Yoneda, Yukio

AU - Nabeshima, Toshitaka

AU - Sawa, Akira

AU - Yamada, Kiyofumi

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