Scholarlink

<p>Methamphetamine (Meth) is a potent central nervous system stimulant with high addictive potential and neurotoxic effects. Chronic use results in significant damage in various brain functions, including cognition, memory, and sensory perception. Olfactory dysfunction is a notable yet often overlooked consequence of Meth abuse, and its underlying mechanisms are not fully understood. This study investigates the mechanisms of Meth-induced olfactory impairment through a thorough examination of olfactory bulb (OB) neurogenesis. We found that chronic Meth abuse impaired olfactory function in mice by not only reducing the self-renewal of subventricular zone (SVZ) neural stem cells (NSCs) but also altering their differentiation potential, leading their differentiation into astrocytes at the expense of neurons. Mechanistically, Meth inhibits autophagosome-lysosome fusion by downregulating Syntaxin 17 (Stx17), which reduces autophagic flux. In NSCs, autophagy tightly regulates Notch1 levels, and impaired autophagic degradation of Notch1 leads to its abnormal activation. This alters NSCs fate determination, ultimately affecting OB neurogenesis. Our study reveals that Meth impairs olfactory function through autophagic dysfunction and aberrant Notch1 signaling. Understanding these mechanisms not only provides new insights into Meth-induced olfactory dysfunction but also offers potential targets for developing therapies to alleviate Meth-induced neurotoxicity and sensory damage in the future.</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

Impaired olfactory bulb neurogenesis mediated by Notch1 contributes to olfactory dysfunction in mice chronically exposed to methamphetamine

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月20日

查看全文
  • Cihang Gu,
  • Zhuo Wang,
  • Wenyu Luo,
  • Haosen Ling,
  • Xilie Cui,
  • Tongtong Deng,
  • Kuan Li,
  • Wei Huang,
  • Qiqian Xie,
  • Bowen Tao,
  • Xiaolan Qi,
  • Xiaojia Peng,
  • Jiuyang Ding,
  • Pingming Qiu

摘要

Methamphetamine (Meth) is a potent central nervous system stimulant with high addictive potential and neurotoxic effects. Chronic use results in significant damage in various brain functions, including cognition, memory, and sensory perception. Olfactory dysfunction is a notable yet often overlooked consequence of Meth abuse, and its underlying mechanisms are not fully understood. This study investigates the mechanisms of Meth-induced olfactory impairment through a thorough examination of olfactory bulb (OB) neurogenesis. We found that chronic Meth abuse impaired olfactory function in mice by not only reducing the self-renewal of subventricular zone (SVZ) neural stem cells (NSCs) but also altering their differentiation potential, leading their differentiation into astrocytes at the expense of neurons. Mechanistically, Meth inhibits autophagosome-lysosome fusion by downregulating Syntaxin 17 (Stx17), which reduces autophagic flux. In NSCs, autophagy tightly regulates Notch1 levels, and impaired autophagic degradation of Notch1 leads to its abnormal activation. This alters NSCs fate determination, ultimately affecting OB neurogenesis. Our study reveals that Meth impairs olfactory function through autophagic dysfunction and aberrant Notch1 signaling. Understanding these mechanisms not only provides new insights into Meth-induced olfactory dysfunction but also offers potential targets for developing therapies to alleviate Meth-induced neurotoxicity and sensory damage in the future.