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<p>Methamphetamine (Meth) abuse leads to cognitive impairment, with the hippocampus being severely affected. However, the precise cellular mechanisms underlying Meth-induced hippocampal damage remain unclear. This study utilizes single-nucleus RNA sequencing (snRNA-seq) to investigate the transcriptional changes in mouse hippocampal neurons after acute Meth exposure. We analyze 36,376 nuclei isolated from the hippocampus of acute Meth-treated and control mice, revealing significant alterations in excitatory neuron transcriptomes. Notably, oxidative phosphorylation (OXPHOS) and peroxisome pathways were prominently activated. Five distinct excitatory neuron subtypes were identified across different hippocampal regions, with the dorsal-ventral (DG) region exhibiting the most pronounced changes in gene expression, inflammatory response, reactive oxygen species (ROS) signaling, and OXPHOS activity. High-dimensional weighted correlation network analysis (hdWGCNA) reveals five modules endowed with functional roles in recognizing-associated pathways. Furthermore, it provides insights into intercellular communication and transcriptional regulation patterns within the hippocampus after Meth exposure. In conclusion, this study offers a comprehensive understanding of Meth’s impact on hippocampal transcriptomes and may guide the development of therapeutic strategies for acute Meth-induced neurotoxicity.</p>

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Single-nucleus RNA sequencing and functional studies of acute methamphetamine-induced cognitive impairment

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月16日

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  • Di An,
  • Fang Lu,
  • Yifei Wang,
  • Zhongman Zhang,
  • Sining Meng,
  • Yanlong Chen,
  • Xiaodong You,
  • Yi Zhu,
  • Wenbo Yuan,
  • Zheng Zhou,
  • Peipei Huang,
  • Jun Wang,
  • Xufeng Chen

摘要

Methamphetamine (Meth) abuse leads to cognitive impairment, with the hippocampus being severely affected. However, the precise cellular mechanisms underlying Meth-induced hippocampal damage remain unclear. This study utilizes single-nucleus RNA sequencing (snRNA-seq) to investigate the transcriptional changes in mouse hippocampal neurons after acute Meth exposure. We analyze 36,376 nuclei isolated from the hippocampus of acute Meth-treated and control mice, revealing significant alterations in excitatory neuron transcriptomes. Notably, oxidative phosphorylation (OXPHOS) and peroxisome pathways were prominently activated. Five distinct excitatory neuron subtypes were identified across different hippocampal regions, with the dorsal-ventral (DG) region exhibiting the most pronounced changes in gene expression, inflammatory response, reactive oxygen species (ROS) signaling, and OXPHOS activity. High-dimensional weighted correlation network analysis (hdWGCNA) reveals five modules endowed with functional roles in recognizing-associated pathways. Furthermore, it provides insights into intercellular communication and transcriptional regulation patterns within the hippocampus after Meth exposure. In conclusion, this study offers a comprehensive understanding of Meth’s impact on hippocampal transcriptomes and may guide the development of therapeutic strategies for acute Meth-induced neurotoxicity.