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PO3-1-97

Involvement of kynurenine pathway in behavioral impairments in the offspring induced by the prenatal poly I: C injection

[Speaker] Moe Niijima:1
[Co-author] Akihiro Mouri:1,4, Tomoaki Teshigawara:2, Kazuo Kunisawa:3, Hisayoshi Kubota:1, Mami Hirakawa:1, Yuko Mori:2, Masato Hoshi:2, Toshitaka Nabeshima:3,4, Kuniaki Saito:2,4
1:Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health Science, Japan, 2:Department of Disease Control and Prevention, Fujita Health University Graduate School of Health Sciences, Japan, 3:Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Sciences, Japan, 4:Japanese Drug Organization of Appropriate Use and Research, Japan

Backgrounds: Epidemiological studies have suggested that viral infection during pregnancy increases the risk for schizophrenia in the adult offspring. Offspring from pregnant mice injected with synthetic dsRNA [poly I:C] exhibit schizophrenia-like behavioral impairments. Kynurenine pathway (KP) is often systematically up-regulated, when the immune response is activated by viral infection. We investigated the involvement of KP in behavioral impairments in the offspring induced by the prenatal poly I:C injection.

Methods: Pregnant C57BL/6J mice were injected with poly I:C (20mg/kg, i.p.) on gestational day 12. Contents of KP metabolites and mRNA levels of KP enzymes in the placenta and fetal brain were measured 24 hours after poly I:C. Adult offspring from pregnant wild-type and kynurenine-3-monooxygenase knock out (KMO KO) mice injected with poly I:C were subjected behavioral tests.

Results: Prenatal injection of poly I:C increased anthranilic acid (AA), but decreased 3-hydroxykynurenine (3HK) in the placenta and fetal brain, and increased 3-hydroxyanthranilic acid (3HAA) in the fetal brain. Adult offspring from pregnant wild-type mice injected with poly I:C showed augmentation of MK-801-induced hyper activity, deficits of sociality and object recognition, although these behavioral impairments are not observed in the adult offspring from pregnant KMO KO mice injected with poly I:C.

Conclusions: These results suggest that KP is involved in behavioral impairments in the offspring induced by the prenatal poly I:C injection.

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