Scholarlink

<p>Psychotic disorder is a significant consequence of ketamine abuse. However, the molecular mechanisms and biomarkers for this psychotic disorder and associated long-term cognitive impairment remain unclear. To investigate the behavioral changes and comprehensive gene expression alterations in mice following ketamine administration, we employed behavioral testing and RNA sequencing (RNA-seq). We further examined the role of dopamine D1 receptor (Drd1) activity in mediating ketamine-induced psychotic-like behavior and its impact on the transcriptome in these mice. Our findings indicated that blocking Drd1 activity with an antagonist mitigated ketamine-induced schizophrenia-like behaviors, while activating Drd1 with an agonist partially replicated these symptoms. Transcriptome analysis of the mouse hippocampus using RNA-seq revealed an enrichment of differentially expressed genes implicated in the GTPase activation pathway. Specifically, both <i>Rgs4</i> and <i>Gnai3</i> were involved in ketamine-induced psychiatric effects. Furthermore, we observed that the mRNA expression of <i>Gnai3</i> was decreased in peripheral blood and the serum levels of eotaxin-2 were elevated two weeks after ketamine administration. These changes suggest that <i>Gnai3</i> and eotaxin-2 may serve as potential biomarkers for ketamine abuse. These results demonstrate the crucial role of Drd1 activity in a mouse model of ketamine-induced schizophrenia-like disorder. The altered expression of Gnai3 in peripheral blood and the elevated levels of cytokine eotaxin-2 in serum indicate their potential as peripheral blood biomarkers for ketamine abuse in mice.</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

Ketamine Alters Specific Gene Expression Profiles by Transcriptome-Wide Responses in a Ketamine-Induced Schizophrenia-Like Mouse Model

  • 期刊论文

  • 发表日期：

    2025年2月24日

查看全文
  • Zhe Du,
  • Xiu-mei Zhu,
  • Peng Lv,
  • Ying Pan,
  • Xi-kai Hou,
  • Ang Li,
  • Dong Zhao,
  • Jia-xin Xing,
  • Jun Yao

摘要

Psychotic disorder is a significant consequence of ketamine abuse. However, the molecular mechanisms and biomarkers for this psychotic disorder and associated long-term cognitive impairment remain unclear. To investigate the behavioral changes and comprehensive gene expression alterations in mice following ketamine administration, we employed behavioral testing and RNA sequencing (RNA-seq). We further examined the role of dopamine D1 receptor (Drd1) activity in mediating ketamine-induced psychotic-like behavior and its impact on the transcriptome in these mice. Our findings indicated that blocking Drd1 activity with an antagonist mitigated ketamine-induced schizophrenia-like behaviors, while activating Drd1 with an agonist partially replicated these symptoms. Transcriptome analysis of the mouse hippocampus using RNA-seq revealed an enrichment of differentially expressed genes implicated in the GTPase activation pathway. Specifically, both Rgs4 and Gnai3 were involved in ketamine-induced psychiatric effects. Furthermore, we observed that the mRNA expression of Gnai3 was decreased in peripheral blood and the serum levels of eotaxin-2 were elevated two weeks after ketamine administration. These changes suggest that Gnai3 and eotaxin-2 may serve as potential biomarkers for ketamine abuse. These results demonstrate the crucial role of Drd1 activity in a mouse model of ketamine-induced schizophrenia-like disorder. The altered expression of Gnai3 in peripheral blood and the elevated levels of cytokine eotaxin-2 in serum indicate their potential as peripheral blood biomarkers for ketamine abuse in mice.