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<p>Accumulating evidence from animals has shown that multiple exposures to general anesthetics during brain development may cause extensive neuronal apoptosis and long-term memory impairments. However, the underlying mechanism is still poorly understood. In the present study, C57BL/6 mice were administered with propofol at postnatal days 19–21. We found that propofol exposure significantly increased neuronal apoptosis in the mouse hippocampal dentate gyrus, as evidenced by cleaved caspase-3 immunofluorescence. Additionally, propofol exposure increased the activation and expression of Ras-related C3 botulinum toxin substrate 1 (Rac1) in the dentate gyrus, as shown by western blotting. Modulating Rac1, either through inhibition or overexpression, was found to mitigate or exacerbate propofol-induced neuronal apoptosis, respectively. We further demonstrated that propofol decreased the expression of the anti-apoptotic protein phosphorylated serine/threonine kinase Akt via Rac1. The results of the open field and Morris water maze test further revealed that silencing Rac1 alleviated propofol-induced cognitive dysfunction. Our findings demonstrated that propofol exposure induced neuronal apoptosis and long-term cognitive dysfunction in the mouse hippocampal dentate gyrus by regulating Rac1.</p>

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Inhibition of Rac1 Attenuated Propofol-Induced Neurotoxicity in the Hippocampal Dentate Gyrus in Developing Mice

  • 期刊论文

  • 发表日期：

    2025年6月25日

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  • Yuan Li,
  • Haifeng Duan,
  • Qi Wang,
  • Yi Lin,
  • Zhoujing Yang,
  • Zhiru Wang,
  • Yingwei Wang,
  • Kai Wei,
  • Daojie Xu

摘要

Accumulating evidence from animals has shown that multiple exposures to general anesthetics during brain development may cause extensive neuronal apoptosis and long-term memory impairments. However, the underlying mechanism is still poorly understood. In the present study, C57BL/6 mice were administered with propofol at postnatal days 19–21. We found that propofol exposure significantly increased neuronal apoptosis in the mouse hippocampal dentate gyrus, as evidenced by cleaved caspase-3 immunofluorescence. Additionally, propofol exposure increased the activation and expression of Ras-related C3 botulinum toxin substrate 1 (Rac1) in the dentate gyrus, as shown by western blotting. Modulating Rac1, either through inhibition or overexpression, was found to mitigate or exacerbate propofol-induced neuronal apoptosis, respectively. We further demonstrated that propofol decreased the expression of the anti-apoptotic protein phosphorylated serine/threonine kinase Akt via Rac1. The results of the open field and Morris water maze test further revealed that silencing Rac1 alleviated propofol-induced cognitive dysfunction. Our findings demonstrated that propofol exposure induced neuronal apoptosis and long-term cognitive dysfunction in the mouse hippocampal dentate gyrus by regulating Rac1.