دورية أكاديمية
Brain iron loading impairs DNA methylation and alters GABAergic function in mice.
| العنوان: | Brain iron loading impairs DNA methylation and alters GABAergic function in mice. |
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| المؤلفون: | Ye Q; Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, USA., Trivedi M; Department of Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, Florida, USA; and., Zhang Y; Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, USA., Böhlke M; Department of Pharmaceutical Sciences, Massachusetts College of Pharmacy and Health Science (MCPHS) University, Boston, Massachusetts, USA., Alsulimani H; Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, USA., Chang J; Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, USA., Maher T; Department of Pharmaceutical Sciences, Massachusetts College of Pharmacy and Health Science (MCPHS) University, Boston, Massachusetts, USA., Deth R; Department of Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, Florida, USA; and., Kim J; Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, USA. |
| المصدر: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2019 Feb; Vol. 33 (2), pp. 2460-2471. Date of Electronic Publication: 2018 Oct 02. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Federation of American Societies for Experimental Biology Country of Publication: United States NLM ID: 8804484 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-6860 (Electronic) Linking ISSN: 08926638 NLM ISO Abbreviation: FASEB J |
| أسماء مطبوعة: | Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley Original Publication: [Bethesda, Md.] : The Federation, [c1987- |
| مواضيع طبية MeSH: | DNA Methylation* , Mutation*, Brain/*metabolism , Brain/*pathology , Hemochromatosis Protein/*physiology , Iron/*metabolism , Receptors, GABA-A/*metabolism, Animals ; Epigenesis, Genetic ; Gene Expression Regulation ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Protein Subunits ; Receptors, GABA-A/genetics |
| مستخلص: | 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 GABA |
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| معلومات مُعتمدة: | K99 ES017781 United States ES NIEHS NIH HHS; R00 ES017781 United States ES NIEHS NIH HHS |
| فهرسة مساهمة: | Keywords: HFE; anxiety; epigenetics; hemochromatosis; oxidative stress |
| المشرفين على المادة: | 0 (HFE protein, human) 0 (Hemochromatosis Protein) 0 (Protein Subunits) 0 (Receptors, GABA-A) E1UOL152H7 (Iron) |
| تواريخ الأحداث: | Date Created: 20181003 Date Completed: 20190826 Latest Revision: 20240214 |
| رمز التحديث: | 20240214 |
| مُعرف محوري في PubMed: | PMC6338660 |
| DOI: | 10.1096/fj.201801116RR |
| PMID: | 30277817 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1530-6860 |
|---|---|
| DOI: | 10.1096/fj.201801116RR |