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Maternal immune activation leads to schizophreniform pathology in rodent offspring :Elucidating a non-inherited schizophrenia onset mechanism
https://repo.qst.go.jp/records/70587
https://repo.qst.go.jp/records/705876e47ecea-b4bd-4c59-9132-8c67a322d4c1
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2011-10-27 | |||||
| タイトル | ||||||
| タイトル | Maternal immune activation leads to schizophreniform pathology in rodent offspring :Elucidating a non-inherited schizophrenia onset mechanism | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Oh-Nishi, Arata
× Oh-Nishi, Arata× et.al× 大西 新 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Schizophrenia is characterized by disturbances of thoughts, perception, cognition and volition. About 1% of the world population becomes morbid with schizophrenia in adolescence. Recently, emerging literature from epidemiological studies has provided evidence that maternal immune activation contributes to the etiology of schizophrenia. For example, several studies have reported the correlation between influenza infection at pregnancy and increased risk of schizophrenia in offspring. Other maternal infectious diseases such as poliovirus and rubella have also shown correlation with increased risk of schizophrenia, suggesting that not a specific viral infection, but rather maternal immune activation itself appears to be a risk factor of schizophrenia. In animal model studies, maternal immune activation revealed behavioral abnormalities in offspring consistent with observations in schizophrenia. For example, immune activation of pregnant rodents by injection of synthetic polyriboinosinic-polyribocytidilic acid (Poly I:C), which mimics viral infection through Toll-like receptor 3 (TLR3) stimulation, causes their offspring to have reduced the hippocmapal synaptic function, working memory, pre-pulse inhibition and latent inhibition, as well as amphetamine hypersensitivity (Oh-Nishi A 2010, Patterson PH 2009). However, it is unclear whether maternal immune activation produces schizophreniform neuronal pathology in the mature offspring. Recently, using in vivo imaging such as positron emission tomography (PET), dopamine receptor functions were investigated in schizophrenia patients brains, and it was reported that dopamine D2 receptor (D2R) binding decreases in the medial prefrontal cortex (mPFC) (Takahashi et al 2006). Thus, using micro PET, we confirmed that the maternal immune activation rodent model demonstrate D2R binding reduction as in schizophrenia patients. We administered TLR3 ligand synthetic double-stranded RNA Poly I:C, which mimics viral infection causing immune activation, to pregnant rats on gestation days 15-18. This resulted in increased pro-inflammatory cytokines such as IL-6, TNF-alpha and IL-1beta (but not IL-2 and IL-10) in maternal sera 3 hours after Poly I:C injection. We then investigated dopamine receptor function of mature offspring of Poly I:C-treated dams by micro PET with D2/D3R specific ligands such as C11-FLB457. We found that dopamine D2/D3 receptor-specific ligand binding potential was significantly decreased in mPFC in mature offspring of Poly I:C-treated dams (P<0.003) by statistical parametric mapping using PET images, in which the number of Parvalbumin-positive cells (P<0.005) but not NeuN positive cells was reduced. It is suggested that D2R dysfunction might underlie parvalbumin-positive inter-neuronal dysfunction in mPFC of schizophrenia patients (Takahashi et al 2006). In this context, the results indicate a high degree of homology between the rodent model of maternal immune activation pathology and schizophrenia patients. We suggest that maternal increases in pro-inflammatory cytokines might be the pathoetiology of non-inherited schizophrenia. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 第３２回内藤コンファレンス | |||||
| 発表年月日 | ||||||
| 日付 | 2011-10-21 | |||||
| 日付タイプ | Issued | |||||
