Artemisinin ameliorates cognitive decline by inhibiting hippocampal neuronal ferroptosis via Nrf2 activation in T2DM mice
Background Neuronal ferroptosis plays a critical role in the pathogenesis of cognitive deficits. The present study explored whether artemisinin protected type 2 diabetes mellitus (T2DM) mice from cognitive impairments by attenuating neuronal ferroptosis in the hippocampal CA1 region. Methods STZ-induced T2DM mice were treated with artemisinin (40 mg/kg, i.p.), or cotreated with artemisinin and Nrf2 inhibitor MEL385 or ferroptosis inducer erastin for 4 weeks. Cognitive performance was determined by the Morris water maze and Y maze tests. Hippocampal ROS, MDA, GSH, and $ Fe^{2+} $ contents were detected by assay kits. Nrf2, p-Nrf2, HO-1, and GPX4 proteins in hippocampal CA1 were assessed by Western blotting. Hippocampal neuron injury and mitochondrial morphology were observed using H&E staining and a transmission electron microscope, respectively. Results Artemisinin reversed diabetic cognitive impairments, decreased the concentrations of ROS, MDA and $ Fe^{2+} $, and increased the levels of p-Nr2, HO-1, GPX4 and GSH. Moreover, artemisinin alleviated neuronal loss and ferroptosis in the hippocampal CA1 region. However, these neuroprotective effects of artemisinin were abolished by Nrf2 inhibitor ML385 and ferroptosis inducer erastin. Conclusion Artemisinin effectively ameliorates neuropathological changes and learning and memory decline in T2DM mice; the underlying mechanism involves the activation of Nrf2 to inhibit neuronal ferroptosis in the hippocampus. Graphical Abstract.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Molecular medicine - 30(2024), 1 vom: 07. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Bo [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
Artemisinin |
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| Anmerkungen: |
© The Author(s) 2024 |
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| doi: |
10.1186/s10020-024-00797-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
SPR05505188X |
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| 245 | 1 | 0 | |a Artemisinin ameliorates cognitive decline by inhibiting hippocampal neuronal ferroptosis via Nrf2 activation in T2DM mice |
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| 520 | |a Background Neuronal ferroptosis plays a critical role in the pathogenesis of cognitive deficits. The present study explored whether artemisinin protected type 2 diabetes mellitus (T2DM) mice from cognitive impairments by attenuating neuronal ferroptosis in the hippocampal CA1 region. Methods STZ-induced T2DM mice were treated with artemisinin (40 mg/kg, i.p.), or cotreated with artemisinin and Nrf2 inhibitor MEL385 or ferroptosis inducer erastin for 4 weeks. Cognitive performance was determined by the Morris water maze and Y maze tests. Hippocampal ROS, MDA, GSH, and $ Fe^{2+} $ contents were detected by assay kits. Nrf2, p-Nrf2, HO-1, and GPX4 proteins in hippocampal CA1 were assessed by Western blotting. Hippocampal neuron injury and mitochondrial morphology were observed using H&E staining and a transmission electron microscope, respectively. Results Artemisinin reversed diabetic cognitive impairments, decreased the concentrations of ROS, MDA and $ Fe^{2+} $, and increased the levels of p-Nr2, HO-1, GPX4 and GSH. Moreover, artemisinin alleviated neuronal loss and ferroptosis in the hippocampal CA1 region. However, these neuroprotective effects of artemisinin were abolished by Nrf2 inhibitor ML385 and ferroptosis inducer erastin. Conclusion Artemisinin effectively ameliorates neuropathological changes and learning and memory decline in T2DM mice; the underlying mechanism involves the activation of Nrf2 to inhibit neuronal ferroptosis in the hippocampus. Graphical Abstract | ||
| 650 | 4 | |a Diabetic cognitive deficit |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Ferroptosis |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Hippocampus |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Artemisinin |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Nrf2 |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Zhu, Sheng |4 aut | |
| 700 | 1 | |a Guo, Miao |4 aut | |
| 700 | 1 | |a Ma, Run-Dong |4 aut | |
| 700 | 1 | |a Tang, Ya-Ling |4 aut | |
| 700 | 1 | |a Nie, Ya-Xiong |4 aut | |
| 700 | 1 | |a Gu, Hong-Feng |0 (orcid)0009-0004-2884-8246 |4 aut | |
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