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P3‐022: Multiple roles for TDP‐43 in tau gene expression regulation
Author(s) -
Simone Roberto,
Kay Victoria,
Hondhamuni Geshanti,
Lees Andrew,
De Silva Rohan
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.1240
Subject(s) - reporter gene , microbiology and biotechnology , biology , gene , transfection , mutant , transcriptional regulation , messenger rna , gene knockdown , western blot , gene expression , genetics
post hoc test applied when appropriate. Data are expressed as mean 6 SD and p< 0.05 was considered statistically significant.Results:Dex produced significant increases in hippocampal p-tau levels at the AT8, CP13, and PHF-1 phosphoepitopes 30 min (0.5h) following treatment (Fig. 1). Interestingly, at 2h post-Dex, a significant increase in p-tau was observed at all three phosphoepitopes despite recovery from anesthesia. No significant changes in total-tau levels were observed following Dex administration. Kinase activation could not explain the increase in p-tau levels; however, significant decreases in demethylation levels of the catalytic subunit of protein phosphastase 2A (PP2A-C) and the A subunit of PP2A (PP2A-A) paralleled the p-tau increase. Conclusions: These data indicate that Dex directly induces tau hyperphosphorylation in the mouse hippocampus. This effect persists after the recovery from anesthesia and may involve the deregulation of PP2A. The impact of this anesthetic exposure on neurofibrillary pathology warrants further investigation.