Activation of Sonic Hedgehog Pathway in Astrocytes by Angiostrongylus cantonensis

Humans and mice are non-permissive hosts of Angiostrongylus cantonensis. After infection, the parasite induces immune responses by eosinophil recruitment and cytokine release (IL-4, IL-5 and eotaxin) through the NF-κB pathway. These changes lead to eosinophilic meningitis and eosinophilic menigoencephalisis. In the infected mouse brains, A. cantonensis causes the production of tremendous oxidative stress, which results in apoptosis and brain injuries. Astrocytes are the most abundant glial cells in the brain. They regulate the migration and differentiation of neural stem cells by releasing cytokines and enzymes. In addition, they delay neuronal cell death due to oxidative stress. Sonic hedgehog signaling (Shh) is an important signaling pathway in tumor cell differentiation and resisting environmental oxidative stress. Shh and its down-stream genes are also biomarkers of oncogenes and tumors. In astrocytes with injuries or under oxidative stress, this signaling pathway is activated and highly expressed. This activation reduces apoptosis of astrocytes and enhance their survival. In our preliminary study, we have demonstrated that the expression levels of Shh-related genes and proteins such as Shh, Ptc, Smo and Gli1 significantly elevate in the brain tissue of mice after A. cantonensis infection. This study is designed to investigate the role of Shh in astrocytes from A. cantonensis-infected mice and the mechanism of regulation using a BALB/c mouse model. After determining the expression of Shh-related proteins in these astrocytes using immunohistochemical techniques, analysis of the excretory/secretory products of the fifth-stage larvae is employed to detect proteins causing ROS generation and apoptosis in astrocytes. By inhibition and over-expression of the shh gene, we can confirm the effectiveness of Shh in reducing oxidative stress and apoptosis of astrocytes after A. cantonensis infection.

Project ID:PC10401-0174
External Project ID:NSC102-2320-B182-028-MY3