Luteolin attenuates interleukin-6-mediated astrogliosis in human iPSC-derived neural aggregates: A candidate preventive substance for maternal immune activation-induced abnormalities

Publication date: 13 July 2017 Source:Neuroscience Letters, Volume 653 Author(s): Masashi Zuiki, Tomohiro Chiyonobu, Michiko Yoshida, Hiroshi Maeda, Satoshi Yamashita, Satoshi Kidowaki, Tatsuji Hasegawa, Hitoshi Gotoh, Tadashi Nomura, Katsuhiko Ono, Hajime Hosoi, Masafumi Morimoto Maternal infection during pregnancy increases the risk of neurodevelopmental conditions such as autism spectrum disorders and schizophrenia in offspring. Several previous animal studies have indicated that maternal immune activation (MIA), rather than a specific pathogen, alters fetal brain development. Among them, prenatal exposure to interleukin-6 (IL-6) has been associated with behavioral and neuropathological abnormalities, though such findings remain to be elucidated in humans. We developed a human cell-based model of MIA by exposing human induced pluripotent stem cells (hiPSCs)-derived neural aggregates to IL-6 and investigated whether luteolin—a naturally occurring flavonoid found in edible plants—could prevent MIA-induced abnormalities. We generated neural aggregates from hiPSCs using the serum-free floating culture of embryoid body-like aggregates with quick reaggregation (SFEBq) method, following which aggregates were cultured in suspension. We then exposed the aggregates to IL-6 (100ng/ml) for 24h at day 51. Transient IL-6 exposure significantly increased the area ratio of astrocytes (GFAP-positive area ratio) and decreased the area ratio of early-born neurons (TBR1-positive ...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research

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