XMU professors identify new pathogenesis of hydrocephalus
Prof. Wang Xin and Prof. Xu Huaxi from the Institute of Neuroscience of XMU recently published their new findings in the Journal of Neuroscience, the proceedings of American Association of Neuroscience and the flagship journal of neuroscience. The paper, entitled SNX27 Deletion Causes Hydrocephalus by Impairing Ependymal Cell Differentiation and Ciliogenesis, discovered that the deficiency of SNX27 can result in the onset and progress of hydrocephalus, and this paper also unveiled the specific molecular mechanism as well as possible treatment for this brain defect.
Hydrocephalus, a common congenital defect, happens to one or two of every 1,000 newborns. Excessive accumlation of cerebrospinal fluid (CSF) could result in high intracranial pressure and bring further complications that may become fatal. Some cases of hydrocephalus are caused by the blockage of the flow of CSF due to skull malformation. The current treatment is primarily to insert surgically a shunt tube to reroute the flow to other parts of the body where CSF can be absorbed. But the downside is that the tube may induce infection, or side effects including headache, vomiting, fever, and allergy. Now it is already confirmed that some cases of hydrocephalus are related to genetic factors, but still very little is known about the gene that causes hydrocephalus and therefore drug targets as well as intervention measures are very limited.
The research team led by Professor Wang and Xu found that the deficiency of SNX27 could induce the congenital hydrocephalus phenotype in the laboratory mice --the lateral ventricles of the mice are filled with CSF and dilate considerably. Further study uncovered that those SNX27-deficient mice lack ependymal cells that normally circulate fluid in the brain.The research also found that SNX27 deletion could lead the neural stem cells in the brain to generate hyperactivated proteins called Notch which can inhibit the differentiation of the neural stem cells into ependymal cells. The activation of NOTCH is mediated by an enzyme called γ-secretase, and the activity of γ-secretase is modulated by SNX27. Injecting inhibitors of γ-secretase/NOTCH in the SNX27 deficient pregnant mice could effectively prevent neonatal mice from the onset of hydrocephalus, giving strong indication that the participation of γ-secretase or NOTCH in developing hydrocephalus. Hence this research provides theoretical support for the future clinical application of the inhibitors of γ-secretase for cases of hydrocephalus caused by the defects of ependymal cells.
The findings are the result of the joint efforts of the research team led by Wang and Xu from the XMU Institute of Neuroscience as well as Sanford Burnham Prebys Medical Discovery Institute of the United States, the Institute of Molecular and Cell Biology affiliated to the Agency for Science, Technology and Research (A*STAR) of Singapore and the College of Medicine of XMU. Up to now, Wang and Xu’s team has achieved a series of amazing achievements, which have been turned into high quality papers that get published in the top-tier international academic journals including Nat Med, Cell Rep, J Neurosci and Mol Neurodegener.
This research has been sponsored by National Natural Science Foundation of China, Recruitment Program of Global Experts (known as the Thousand Talents Plan) initiated by the Organizational Department of the Communist Party of China as well as the President Fund of XMU.
Edited by Long Jin
Read the research paper at http://www.jneurosci.org/content/36/50/12586.abstract