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<p>Seizures induce significant immune and metabolic stress in microglia, but the interaction between these processes remains unclear. This study, utilizing single-nucleus RNA sequencing data from temporal lobe epilepsy (TLE) patients, reveals that reactive oxygen species (ROS) stabilize hypoxia-inducible factor 1-alpha (HIF-1α), thereby inducing glycometabolic reprogramming in microglia and driving the development of a pro-inflammatory phenotype. To address this, a coordination acid-engineered Prussian Blue (PB@ZIF) nanosystem is developed, where Zn²⁺ sites in the zeolitic imidazolate framework (ZIF) lower the local pKa, thereby enhancing the reaction efficiency of PB with free radicals. In vivo experiments using a TLE model demonstrate that PB@ZIF is effectively internalized by microglia and significantly alleviates spontaneous recurrent seizures and seizure-related behaviors. PB@ZIF mitigates microglial inflammatory activation and reduces neuronal injury. Notably, PB@ZIF-induced ROS reduction enhances the enzymatic activity of prolyl hydroxylase domain enzymes, effectively inhibiting HIF-1α-driven glycometabolic reprogramming in microglia. This study identifies a molecular mechanism underlying the immune-metabolic interactions in epilepsy and proposes a promising therapeutic strategy regulating microglial metabolism to improve epilepsy management.</p>

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Coordination acid-engineered Prussian Blue affects glycometabolic reprogramming in microglia for epileptic treatment

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月11日

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  • Yao Zhao,
  • Feixiang Chen,
  • Chen Chen,
  • Yuling Yang,
  • Luo Wang,
  • Jiaqi Zhu,
  • Xin Wang,
  • Yanyan Liu,
  • Jing Ding

摘要

Seizures induce significant immune and metabolic stress in microglia, but the interaction between these processes remains unclear. This study, utilizing single-nucleus RNA sequencing data from temporal lobe epilepsy (TLE) patients, reveals that reactive oxygen species (ROS) stabilize hypoxia-inducible factor 1-alpha (HIF-1α), thereby inducing glycometabolic reprogramming in microglia and driving the development of a pro-inflammatory phenotype. To address this, a coordination acid-engineered Prussian Blue (PB@ZIF) nanosystem is developed, where Zn²⁺ sites in the zeolitic imidazolate framework (ZIF) lower the local pKa, thereby enhancing the reaction efficiency of PB with free radicals. In vivo experiments using a TLE model demonstrate that PB@ZIF is effectively internalized by microglia and significantly alleviates spontaneous recurrent seizures and seizure-related behaviors. PB@ZIF mitigates microglial inflammatory activation and reduces neuronal injury. Notably, PB@ZIF-induced ROS reduction enhances the enzymatic activity of prolyl hydroxylase domain enzymes, effectively inhibiting HIF-1α-driven glycometabolic reprogramming in microglia. This study identifies a molecular mechanism underlying the immune-metabolic interactions in epilepsy and proposes a promising therapeutic strategy regulating microglial metabolism to improve epilepsy management.