TY - JOUR
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
N1 - Funding Information:
We thank Drs. Pamela Talalay and Akiko Takagi-Hayashi for critical reading of this manuscript. 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, Takeda Science Foundation , AstraZeneca Research Grant 2008, and by JST, CREST. NIH grants of MH-084018, MH-069853, as well as grants from Stanley, CHDI, HighQ, S-R, and NARSAD support AS.
PY - 2010/1/5
Y1 - 2010/1/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbr.2009.08.027
DO - 10.1016/j.bbr.2009.08.027
M3 - Article
C2 - 19716847
AN - SCOPUS:70350183754
SN - 0166-4328
VL - 206
SP - 32
EP - 37
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 1
ER -