Scholarlink

<p>Bipolar disorder (BD) is increasingly recognized as a disease with both mitochondrial dysfunction and heightened inflammatory reactivity, yet contribution to neuronal activity remains unclear. To address these gaps, this study utilizes iPSC-derived cerebral organoids (COs) from BD patients and healthy controls to model disease-specific metabolic and inflammatory dysfunction in a more physiologically relevant system. BD COs exhibited mitochondrial impairment, dysregulated metabolic function, and increased nod-leucine rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome activation sensitivity. Treatment with MCC950, a selective NLRP3 inhibitor, effectively rescued mitochondrial function and reduced inflammatory activation in both BD and control COs. The effect of a Bioactive Flavonoid Extract (BFE), a potential therapeutic, was also explored and yielded a partial rescue of inflammasome activation. These findings highlight a mitochondria-inflammasome axis in BD pathophysiology and establish a novel platform for studying BD-associated cellular mechanisms, ultimately bridging the gap between molecular dysfunction and therapeutic development.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

iPSC-derived cerebral organoids reveal mitochondrial, inflammatory and neuronal vulnerabilities in bipolar disorder

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月25日

查看全文
  • Dana El Soufi El Sabbagh,
  • Alencar Kolinski Machado,
  • Lauren Pappis,
  • Erika Leigh Beroncal,
  • Delphine Ji,
  • George Nader,
  • Prathyusha Ravi Chander,
  • Jaehyoung Choi,
  • Angela Duong,
  • Hyunjin Jeong,
  • Bruna Panizzutti,
  • Chiara Cristina Bortolasci,
  • Andrea Szatmari,
  • Peter Carlen,
  • Margaret Hahn,
  • Liliana Attisano,
  • Michael Berk,
  • Ken Walder,
  • Ana Cristina Andreazza

摘要

Bipolar disorder (BD) is increasingly recognized as a disease with both mitochondrial dysfunction and heightened inflammatory reactivity, yet contribution to neuronal activity remains unclear. To address these gaps, this study utilizes iPSC-derived cerebral organoids (COs) from BD patients and healthy controls to model disease-specific metabolic and inflammatory dysfunction in a more physiologically relevant system. BD COs exhibited mitochondrial impairment, dysregulated metabolic function, and increased nod-leucine rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome activation sensitivity. Treatment with MCC950, a selective NLRP3 inhibitor, effectively rescued mitochondrial function and reduced inflammatory activation in both BD and control COs. The effect of a Bioactive Flavonoid Extract (BFE), a potential therapeutic, was also explored and yielded a partial rescue of inflammasome activation. These findings highlight a mitochondria-inflammasome axis in BD pathophysiology and establish a novel platform for studying BD-associated cellular mechanisms, ultimately bridging the gap between molecular dysfunction and therapeutic development.