Department of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of ICU, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
CNS Neurosci Ther. 2023 Jan;29(1):306-316. doi: 10.1111/cns.14004. Epub 2022 Oct 25.
Exposure to anesthesia leads to extensive neurodegeneration and long-term cognitive deficits in the developing brain. Caenorhabditis elegans also shows persistent behavioral changes during development after exposure to anesthetics. Clinical and rodent studies have confirmed that altered expression of the regulators of G protein signaling (RGS) in the nervous system is a factor contributing to neurodegenerative and psychological diseases. Evidence from preclinical studies has suggested that RGS controls drug-induced plasticity, including morphine tolerance and addiction. This study aimed to observe the effect of propofol exposure in the neurodevelopmental stage on learning and memory in the L4 stage and to study whether this effect is related to changes in rgs-3 expression.
Caenorhabditis elegans were exposed to propofol at the L1 stage, and learning and memory abilities were observed at the L4 stage. The expression of rgs-3 and the nuclear distribution of EGL-4 were determined to study the relevant mechanisms. Finally, RNA interference was performed on rgs-3-expressing cells after propofol exposure. Then, we observed their learning and memory abilities.
Propofol time- and dose-dependently impaired the learning capacity. Propofol induced a decline in non-associative and associative long-term memory, rgs-3 upregulation, and a failure of nuclear accumulation of EGL-4/PKG in AWC neurons. Inhibition of rgs-3 could alleviate the propofol-induced changes.
Inhibition of the expression of rgs-3 alleviated propofol-induced learning and memory deficits in Caenorhabditis elegans.
麻醉暴露会导致发育中的大脑广泛的神经退行性变和长期认知缺陷。秀丽隐杆线虫在暴露于麻醉剂后，其发育过程中也会出现持续的行为改变。临床和啮齿动物研究证实，神经系统中 G 蛋白信号调节因子 (RGS) 的表达改变是导致神经退行性和心理疾病的一个因素。来自临床前研究的证据表明，RGS 控制着药物诱导的可塑性，包括吗啡耐受和成瘾。本研究旨在观察神经发育阶段暴露于异丙酚对 L4 阶段学习和记忆的影响，并研究这种影响是否与 rgs-3 表达的变化有关。
秀丽隐杆线虫在 L1 阶段暴露于异丙酚，在 L4 阶段观察学习和记忆能力。测定 rgs-3 的表达和 EGL-4 的核分布，以研究相关机制。最后，在异丙酚暴露后对 rgs-3 表达细胞进行 RNA 干扰，然后观察它们的学习和记忆能力。
异丙酚时间和剂量依赖性地损害了学习能力。异丙酚诱导非联想性和联想性长时记忆下降，rgs-3 上调，AWC 神经元中 EGL-4/PKG 的核积累失败。rgs-3 的抑制可减轻异丙酚诱导的变化。
抑制 rgs-3 的表达可减轻异丙酚诱导的秀丽隐杆线虫学习和记忆缺陷。
