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

研究成果: Article

106 引用 (Scopus)


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.

ジャーナルBehavioural Brain Research
出版物ステータスPublished - 05-01-2010


All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience


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, 206(1), 32-37.