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<p>Mitochondrial dysfunction, often linked to the deregulation of mitochondrial biogenesis, plays a significant role in the progression of neurological diseases. Dexmedetomidine (Dex), a selective alpha-2 adrenergic agonist utilized for anesthesia and sedation, has a largely unexplored impact on mitochondrial function. In this study, cells were treated with Dex at concentrations of 10 μg/mL and 20 μg/mL. Mitochondrial function was assessed by measuring mitochondrial membrane potential, adenosine triphosphate (ATP) production, and oxygen consumption rates. The expression levels of key mitochondrial genes and proteins were analyzed using quantitative polymerase chain reaction (qPCR) and Western blot. To investigate the role of AMP-activated protein kinase α (AMPK), cells were co-treated with the AMPK inhibitor Compound C. Our results demonstrate that treating cells with Dex significantly enhances mitochondrial membrane potential, ATP production, and oxygen consumption rates. Additionally, Dex increases the expression of vital mitochondrial genes, including Mitochondrially Encoded NADH: Ubiquinone Oxidoreductase Core Subunit 6 (mtND6), Mitochondrially Encoded Cytochrome c Oxidase II (mtCO2), and Mitochondrially Encoded ATP Synthase 6 (mtATP6), while also improving the mtDNA-to-nDNA ratio. The treatment raises Messenger Ribonucleic Acid (mRNA) and protein levels of essential mitochondrial biogenesis regulators such as Nuclear Respiratory Factor 1(Nrf1), Mitochondrial Transcription Factor A (TFAM), Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1α (PGC-1α), and phosphorylated AMP-Activated Protein Kinase α (p-AMPKα). However, when cells are co-treated with the AMPK inhibitor compound C, these positive effects are lost, highlighting the necessity of AMPK activation for the mitochondrial enhancements induced by Dex. These findings suggest a promising therapeutic potential for Dex in supporting neuronal function through mitochondrial pathways.</p>

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Dexmedetomidine preserves neuronal function by promoting mitochondrial biogenesis through the AMPK/PGC-1α pathway

  • 期刊论文

  • 发表日期：

    2025年7月7日

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  • Li Wang,
  • Meng Zhang,
  • Shaowei Wang,
  • Zhen Xing,
  • Tong Jia,
  • Xiaojia Sun,
  • Hui Liu,
  • Jie Yao,
  • Yanlin Chen

摘要

Mitochondrial dysfunction, often linked to the deregulation of mitochondrial biogenesis, plays a significant role in the progression of neurological diseases. Dexmedetomidine (Dex), a selective alpha-2 adrenergic agonist utilized for anesthesia and sedation, has a largely unexplored impact on mitochondrial function. In this study, cells were treated with Dex at concentrations of 10 μg/mL and 20 μg/mL. Mitochondrial function was assessed by measuring mitochondrial membrane potential, adenosine triphosphate (ATP) production, and oxygen consumption rates. The expression levels of key mitochondrial genes and proteins were analyzed using quantitative polymerase chain reaction (qPCR) and Western blot. To investigate the role of AMP-activated protein kinase α (AMPK), cells were co-treated with the AMPK inhibitor Compound C. Our results demonstrate that treating cells with Dex significantly enhances mitochondrial membrane potential, ATP production, and oxygen consumption rates. Additionally, Dex increases the expression of vital mitochondrial genes, including Mitochondrially Encoded NADH: Ubiquinone Oxidoreductase Core Subunit 6 (mtND6), Mitochondrially Encoded Cytochrome c Oxidase II (mtCO2), and Mitochondrially Encoded ATP Synthase 6 (mtATP6), while also improving the mtDNA-to-nDNA ratio. The treatment raises Messenger Ribonucleic Acid (mRNA) and protein levels of essential mitochondrial biogenesis regulators such as Nuclear Respiratory Factor 1(Nrf1), Mitochondrial Transcription Factor A (TFAM), Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1α (PGC-1α), and phosphorylated AMP-Activated Protein Kinase α (p-AMPKα). However, when cells are co-treated with the AMPK inhibitor compound C, these positive effects are lost, highlighting the necessity of AMPK activation for the mitochondrial enhancements induced by Dex. These findings suggest a promising therapeutic potential for Dex in supporting neuronal function through mitochondrial pathways.