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Revealing the Ferroptotic Phenotype of Medulloblastoma
Published on: March 15, 2024
Enriched Environment Suppresses Neuronal Ferroptosis Through SIRT1/AKT/GSK3β-Dependent Glycogen Metabolic
Bao Zhou1, Yixi Hao1, Pengkun Yang1
1Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China.
Antioxidants (Basel, Switzerland)
|May 27, 2026
Summary
An enriched environment (EE) protects the brain from stroke-induced ferroptosis by regulating glycogen metabolism via the SIRT1/AKT/GSK3β pathway, offering a new therapeutic target.
Area of Science:
- Neuroscience
- Metabolic pathways
- Cellular biology
Background:
- Neuronal ferroptosis contributes to brain injury after cerebral ischemia.
- The metabolic mechanisms of ferroptosis and enriched environment (EE) neuroprotection are unclear.
- EE may protect against ischemia-induced ferroptosis via glycogen metabolism.
Purpose of the Study:
- To investigate if EE influences ferroptosis-associated pathways through Sirtuin 1 (SIRT1)/protein kinase B (AKT)/glycogen synthase kinase-3β (GSK3β) mediated glycogen metabolism.
- To elucidate the molecular mechanisms of EE-induced cerebroprotection.
Main Methods:
- Mouse model of middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) cellular model.
- Behavioral assessments, molecular and biochemical analyses, and pharmacological interventions.
- Sirtuin 1 (SIRT1) inhibition and overexpression studies.
Main Results:
- EE improved neurological outcomes and reduced infarct volume post-ischemia.
- EE activated the SIRT1/AKT pathway, increased GSK3β inhibitory phosphorylation, and elevated brain glycogen levels.
- SIRT1 inhibition reduced EE's neuroprotective effects; SIRT1 overexpression attenuated ferroptosis in vitro.
Conclusions:
- EE attenuates ferroptosis possibly through SIRT1/AKT/GSK3β-dependent glycogen metabolic remodeling.
- SIRT1-centered regulation of glycogen metabolism is a potential therapeutic target for ischemic stroke.
- EE-induced cerebroprotection offers a novel metabolic perspective.