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- W2894773478 abstract "Iron deficiency is closely associated with altered GABA metabolism and affective behavior. While mutation in the hemochromatosis (HFE) gene disrupts iron homeostasis and promotes oxidative stress that increases the risk of neurodegeneration, it is largely unknown whether HFE mutation modifies GABAergic homeostasis and emotional behavior. The goal of our study was to investigate the impact of HFE on GABAergic neurochemistry and redox–epigenetic regulation in the brain using H67D HFE-mutant mice that recapitulates the H63D-HFE mutation in humans. H67D mice displayed elevated redox-active iron levels in the brain by 32% compared to age-matched wild-type mice. Moreover, the H67D brain had increased isoprostane and decreased glutathione, indicating elevated oxidative stress. Additionally, the H67D brain had decreased global methylation and attenuated DNA methyltransferase (DNMT) activity. Direct addition of iron to purified DNMT in vitro decreased enzyme activity in a concentration-dependent manner. Last, H67D mice exhibited decreased anxiety-like behavior, which was associated with increased expression of the GABAA receptor α2 subunits by 93%, and these changes were also observed in H67D mice fed a low-iron diet. Taken together, our results suggest a putative role of HFE in regulating labile iron status in the brain, and mutation in H67D perturbs redox-methylation status, contributing to GABAergic dysfunction.—Ye, Q., Trivedi, M., Zhang, Y., Böhlke, M., Alsulimani, H., Chang, J., Maher, T., Deth, R., Kim, J. Brain iron loading impairs DNA methylation and alters GABAergic function in mice. FASEB J. 33, 2460–2471 (2019). www.fasebj.org" @default.
- W2894773478 created "2018-10-12" @default.
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- W2894773478 date "2018-10-02" @default.
- W2894773478 modified "2023-10-12" @default.
- W2894773478 title "Brain iron loading impairs DNA methylation and alters GABAergic function in mice" @default.
- W2894773478 cites W1506138247 @default.
- W2894773478 cites W179465749 @default.
- W2894773478 cites W1946377991 @default.
- W2894773478 cites W1963689381 @default.
- W2894773478 cites W1964948396 @default.
- W2894773478 cites W1965375794 @default.
- W2894773478 cites W1965501136 @default.
- W2894773478 cites W1965571310 @default.
- W2894773478 cites W1965672724 @default.
- W2894773478 cites W1969786859 @default.
- W2894773478 cites W1971924540 @default.
- W2894773478 cites W1975497763 @default.
- W2894773478 cites W1981216437 @default.
- W2894773478 cites W1983459339 @default.
- W2894773478 cites W1983883528 @default.
- W2894773478 cites W1990198449 @default.
- W2894773478 cites W1990739193 @default.
- W2894773478 cites W1996240756 @default.
- W2894773478 cites W2003713557 @default.
- W2894773478 cites W2009267659 @default.
- W2894773478 cites W2013868882 @default.
- W2894773478 cites W2016731602 @default.
- W2894773478 cites W2016817836 @default.
- W2894773478 cites W2018659765 @default.
- W2894773478 cites W2020751657 @default.
- W2894773478 cites W2020870274 @default.
- W2894773478 cites W2023831307 @default.
- W2894773478 cites W2026421203 @default.
- W2894773478 cites W2027163659 @default.
- W2894773478 cites W2028164957 @default.
- W2894773478 cites W2029649014 @default.
- W2894773478 cites W2036848594 @default.
- W2894773478 cites W2040570303 @default.
- W2894773478 cites W2042138417 @default.
- W2894773478 cites W2048342066 @default.
- W2894773478 cites W2051521732 @default.
- W2894773478 cites W2055992515 @default.
- W2894773478 cites W2060075607 @default.
- W2894773478 cites W2060446375 @default.
- W2894773478 cites W2062307936 @default.
- W2894773478 cites W2062742764 @default.
- W2894773478 cites W2063817868 @default.
- W2894773478 cites W2067011924 @default.
- W2894773478 cites W2068337287 @default.
- W2894773478 cites W2069780496 @default.
- W2894773478 cites W2071399511 @default.
- W2894773478 cites W2071967920 @default.
- W2894773478 cites W2072605705 @default.
- W2894773478 cites W2082665963 @default.
- W2894773478 cites W2092597346 @default.
- W2894773478 cites W2093685823 @default.
- W2894773478 cites W2093903971 @default.
- W2894773478 cites W2103979587 @default.
- W2894773478 cites W2107277218 @default.
- W2894773478 cites W2112109116 @default.
- W2894773478 cites W2112881162 @default.
- W2894773478 cites W2123334062 @default.
- W2894773478 cites W2128025482 @default.
- W2894773478 cites W2130331036 @default.
- W2894773478 cites W2133501530 @default.
- W2894773478 cites W2133579959 @default.
- W2894773478 cites W2136104345 @default.
- W2894773478 cites W2140190549 @default.
- W2894773478 cites W2142695282 @default.
- W2894773478 cites W2154456419 @default.
- W2894773478 cites W2157215879 @default.
- W2894773478 cites W2158380218 @default.
- W2894773478 cites W2163364365 @default.
- W2894773478 cites W2167979686 @default.
- W2894773478 cites W2169714384 @default.
- W2894773478 cites W2170762845 @default.
- W2894773478 cites W2191557437 @default.
- W2894773478 cites W2192080449 @default.
- W2894773478 cites W2208844090 @default.
- W2894773478 cites W2226694930 @default.
- W2894773478 cites W2259119153 @default.
- W2894773478 cites W2325267338 @default.
- W2894773478 cites W2331643040 @default.
- W2894773478 cites W2336418363 @default.
- W2894773478 cites W2396676014 @default.
- W2894773478 cites W2401079231 @default.
- W2894773478 cites W2466088279 @default.
- W2894773478 cites W2559096096 @default.
- W2894773478 cites W2735612947 @default.