Microtubule Abnormalities Underlying Gulf War Illness in Neurons from Human Induced Pluripotent Cells
Technical Report,01 Sep 2015,31 Aug 2017
Drexel University Philadelphia United States
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The study plan is to develop immortalized cultures of cells from the blood of veterans who are suffering from Gulf War Illness GWI. A simple blood sample is taken from the soldier, and then transduced, using reliable established methods, to make the cells pluripotent. The pluripotent cells lines can then be treated with growth factors to differentiate them into a number of different cell types including neurons. The investigators will develop these cell lines from veterans of the Gulf War who got sick and also from veterans who did not get sick, so the two can be compared. Other scientists studying GWI will be able to use the cell lines for their own studies, which will maximize the effort of the biomedical community to rush medicines and treatment regimens to the veterans who are suffering. At the time of the final report, the pluripotent cell lines had been developed, stored in a repository, and their existence and availability made public through a publication in high visibility medical journal. That publication also provided a details on the rationale for creating the cell lines and how they can be used to address mechanistic questions about GWI, and test potential therapies. The second aim of the funded proposal was to use microtubule-based strategies to correct cellular defects observed in the cell lines when they are exposed to a toxicant regimen designed to mimic GWI. While no studies of this kind were performed on the cells lines created from the Gulf War veterans, because they were not yet ready when the microtubule work had to begin, those studies used pluripotent cell lines from non-veteran humans, as well as primary rodent cell lines. The results, published in a high-impact scientific journal, indicate that inhibitors of HDAC6, the chief microtubule de-acetylase in vertebrate cells, can correct a variety of cellular abnormalities resulting from the GWI toxicant regimen, including defects in dopamine release.
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