Flavonoids, a prenatal prophylaxis via targeting JAK2/STAT3 signaling to oppose IL-6/MIA associated autism.
Flavonoids, a prenatal prophylaxis via targeting JAK2/STAT3 signaling to oppose IL-6/MIA associated autism.
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DOI：
10.1016/j.jneuroim.2009.08.012
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发表时间：
2009-12-10
影响因子：
3.3
通讯作者：
Tan J
中科院分区：
文献类型：
--
作者：
Parker-Athill E;Luo D;Bailey A;Giunta B;Tian J;Shytle RD;Murphy T;Legradi G;Tan J
母体免疫激活（MIA）可以影响胎儿大脑发育，从而影响年轻和成年后代的行为。有报道表明，母体血清中白细胞介素-6（IL-6）的增加在改变胎儿大脑发育方面发挥着关键作用，并可能损害后代的社会行为。有趣的是，这些作用可以通过阻断IL-6来减弱。本研究探讨了柑橘类黄酮木樨草素及其结构类似物地奥司明对IL-6诱导的JAK 2/STAT 3（Janus tyrosine kinase-2/signal transducer and activator of transcription-3）磷酸化和信号传导以及MIA后代行为表型的影响。木犀草素和地奥司明抑制神经元JAK 2/STAT 3磷酸化在体外和体内后IL-6的挑战，以及显着减少行为缺陷的社会互动。重要的是，我们的结果表明地奥司明（10 mg/kg/天）能够阻断STAT 3信号通路;显著对抗MIA/成年后代中MIA诱导的异常行为和神经病理学异常。地奥司明对JAK 2/STAT 3通路的分子抑制可能是减轻IL-6/MIA成年后代中异常社会相互作用的基础。
Maternal immune activation (MIA) can affect fetal brain development and thus behavior of young and adult offspring. Reports have shown that increased Interleukin-6 (IL-6) in the maternal serum plays a key role in altering fetal brain development, and may impair social behaviors in the offspring. Interestingly, these effects could be attenuated by blocking IL-6. The current study investigated the effects of luteolin, a citrus bioflavonoid, and its structural analog, diosmin, on IL-6 induced JAK2/STAT3 (Janus tyrosine kinase-2/signal transducer and activator of transcription-3) phosphorylation and signaling as well as behavioral phenotypes of MIA offspring. Luteolin and diosmin inhibited neuronal JAK2/STAT3 phosphorylation both in vitro and in vivo following IL-6 challenge as well as significantly diminishing behavioral deficits in social interaction. Importantly, our results showed that diosmin (10 mg/kg day) was able to block the STAT3 signal pathway; significantly opposing MIA-induced abnormal behavior and neuropathological abnormalities in MIA/adult offspring. Diosmin’s molecular inhibition of JAK2/STAT3 pathway may underlie the attenuation of abnormal social interaction in IL-6/MIA adult offspring.
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DOI：
10.1016/j.ijdevneu.2004.05.005
发表时间：
2005-04-01
影响因子：
1.8
作者：
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影响因子：
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