High expression of Endogenous Retroviruses from intrauterine life to adulthood in two mouse models of Autism Spectrum Disorders

Figures

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  Figure 1. Transcriptional activity of ETnI, ETnII-α, ETnII-β, ETnII-γ, IAP and MusD genes in whole embryos and, from the offspring, in blood and brain samples obtained from BTBR and C57BL6/J mice. The ERVs expression profile in whole embryos (panel A–F) at gestational days 10.5, in blood (panel A’–F’) and brain (panel A”–F”) samples at post natal day 1, 7, 23 and 120 from BTBR (red box plots) and C57BL6/J (white box plots) mice, was examined by real time-PCR; depicting mild (black dot) and extreme (asterisk) outliers for each group were showed. In BTBR embryos and in blood and in brain samples, the expression levels of all ERVs, were significantly higher with respect to C57BL6/J mice.

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  Figure 2. Expression levels of IL-1β, IL-6, TNF-α, TLR3 and TLR4 genes in whole embryos and, from the offspring, in blood and brain samples obtained from BTBR and C57BL6/J mice. The cytokines and TLRs expression in whole embryos (panel A–E) at gestational days 10.5, in blood (panel A’–E’) and brain samples (panel A”–E”) at post natal day 1 and 7 from BTBR (red box plots) and C57BL6/J (white box plots) mice, was examined by real time-PCR; depicting mild (black dot) and extreme (asterisk) outliers for each group were showed. In the BTBR embryos and in blood and brain samples, higher levels of cytokines and Toll-like receptors expression than in age-matched C57BL/J controls were detected.

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  Figure 3. Transcriptional activity of ETnI, ETnII-α, ETnII-β, ETnII-γ, IAP and MusD genes in whole embryos and, from the offspring, in blood and brain samples obtained from VPA- and vehicle-treated CD-1 mice. The ERVs expression profile in whole embryos (panel A–F) explanted 3 and 24 hours post the treatment, in blood (panel A’–F’) and brain (panel A”–F”) samples obtained at post natal day 1, 7, 23 and 120, was examined by real time-PCR and represented as box plots, depicting mild (black dot) and extreme (asterisk) outliers for each group. In whole embryos higher transcriptional activity of all ERVs analysed in VPA groups (blue box plots) than in vehicle groups (white box plots) was evident, at both time points. In blood, VPA-treated mice (blue box plots) showed higher transcriptional levels of all ERVs than in age-matched controls (white box plots), at post natal day 1 and 7, while in brain at each age points.

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  Figure 4. Expression levels of IL-1β, IL-6, TNF-α, TLR3 and TLR4 genes in whole embryos and, from the offspring, in blood and brain samples from VPA- and vehicle- treated CD-1 dams. The cytokines and TLRs expression in whole embryos (panel A–E) explanted 3 and 24 hours post the treatment, in blood (panel A’–E’) and brain (panel A”–E”) samples obtained at post natal day 1 and 7 from VPA- and vehicle- treated CD-1 dams, was evaluated by real time-PCR and represented as box plots, depicting mild (black dot) and extreme (asterisk) outliers for each group. Prenatal exposure to VPA at gestational day 10.5 increased cytokines expression in embryos (blue box plots), already from 3 hours post treatment than in controls (white box plots). In blood and in brain, also the expression levels of TLRs were higher in VPA mice (blue box plots) than in controls (white box plots).