Flavonoids, a Prenatal Prophylaxis via Targeting JAK2/STAT3 Signaling to Oppose IL-6/Mia Associated Autism
Document Type
Article
Publication Date
12-10-2009
Description
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.
Citation Information
Parker-Athill, Ellisa; Luo, Deyan; Bailey, Antoinette; Giunta, Brian; Tian, Jun; Shytle, R. Douglas; Murphy, Tanya; Legradi, Gabor; and Tan, Jun. 2009. Flavonoids, a Prenatal Prophylaxis via Targeting JAK2/STAT3 Signaling to Oppose IL-6/Mia Associated Autism. Journal of Neuroimmunology. Vol.217(1-2). 20-27. https://doi.org/10.1016/j.jneuroim.2009.08.012 PMID: 19766327 ISSN: 0165-5728