Erythropoietin ameliorates cognitive dysfunction in mice with type 2 diabetes mellitus via inhibiting iron overload and ferroptosis.

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  • Additional Information
    • Source:
      Publisher: Academic Press Country of Publication: United States NLM ID: 0370712 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2430 (Electronic) Linking ISSN: 00144886 NLM ISO Abbreviation: Exp Neurol Subsets: MEDLINE
    • Publication Information:
      Publication: Orlando Fl : Academic Press
      Original Publication: New York.
    • Subject Terms:
      Ferroptosis* ; Diabetes Mellitus, Type 2*/complications ; Diabetes Mellitus, Type 2*/drug therapy ; Diabetes Mellitus, Experimental*/complications ; Diabetes Mellitus, Experimental*/drug therapy ; Diabetes Mellitus, Experimental*/metabolism ; Erythropoietin*/therapeutic use ; Erythropoietin*/pharmacology ; Cognitive Dysfunction*/drug therapy ; Cognitive Dysfunction*/etiology ; Iron Overload*/complications ; Iron Overload*/drug therapy; Mice ; Animals ; Epoetin Alfa
    • Abstract:
      Type 2 diabetes mellitus (T2DM) is strongly associated with an increased risk of developing cognitive dysfunction. Numerous studies have indicated that erythropoietin (EPO) has neurotrophic effects. Ferroptosis has been reported to be associated with diabetic cognitive dysfunction. However, the impact of EPO on T2DM-associated cognitive dysfunction and its protective mechanism remain unclear. To evaluate the effects of EPO on diabetes-associated cognitive dysfunction, we constructed a T2DM mouse model and found that EPO not only decreased fasting blood glucose but also ameliorated hippocampal damage in the brain. The Morris water maze test indicated that EPO improved cognitive impairments in diabetic mice. Moreover, a ferroptosis inhibitor improved cognitive dysfunction in mice with T2DM in vivo. Furthermore, a ferroptosis inhibitor, but not other cell death inhibitors, mostly rescued high-glucose damaged PC12 cell viability. EPO had a similar effect as the ferroptosis inhibitor, which increased cell viability in the presence of a ferroptosis inducer. In addition, EPO reduced lipid peroxidation, iron levels, and regulated ferroptosis-related expression of proteins in vivo and in vitro. These findings indicate that EPO ameliorates T2DM-associated cognitive dysfunction, which might be related to decreasing iron overload and inhibiting ferroptosis.
      Competing Interests: Declaration of Competing Interest The authors declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2023 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Cognitive dysfunction; Erythropoietin; Ferroptosis; Iron overload; Type 2 diabetes mellitus
    • Accession Number:
      11096-26-7 (Erythropoietin)
      64FS3BFH5W (Epoetin Alfa)
    • Publication Date:
      Date Created: 20230419 Date Completed: 20230522 Latest Revision: 20230524
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.expneurol.2023.114414
    • Accession Number:
      37075971