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化学合成的psilocybin和迷幻提取物对小鼠大脑中的分子和代谢概况的影响

Orr Shahar¹, Alexander Botvinnik¹, Amit Shwartz¹

¹Biological Psychiatry Laboratory and Hadassah BrainLabs Center for Psychedelic Research, Hadassah Medical Center, Hebrew University, Jerusalem, Israel.

Molecular psychiatry

|February 21, 2024

概括

与合成的psilocybin (PSIL) 相比,迷幻提取物 (PME) 对大脑突触可塑性表现出更强烈,更持久的效果. 代谢数据也表明了效果的梯度,这表明PME可能提供了增强的治疗潜力.

科学领域:

神经科学是一个神经科学.
药理学药理学是指药理学的学科.
精神病学是一个精神病学.

背景情况:

三胺类化合物的前药物psilocybin正在接受治疗精神疾病的研究.
临床前数据表明,含有psilocybin的提取物 (PME) 和合成psilocybin (PSIL) 之间的生物效应可能存在差异.

研究的目的:

为了比较PME和PSIL对头部抽反应 (HTR),神经可塑性相关的突触蛋白和小鼠前皮层代谢概况的影响.
调查PME和PSIL之间生物活性和治疗功效的潜在差异.

主要方法:

雄性C57Bl/6j小鼠接受了PME或PSIL的治疗.
头部抽反应 (HTR) 在20分钟内被测量.
在大脑样本 (额叶皮层,海马体,杏仁体,条纹体) 中,使用治疗后3天和11天的西部斑点分析了突触蛋白 (GAP43,PSD95,synaptophysin,SV2A).
额叶皮层的代谢概况使用毛细管电泳-里埃转换质谱法 (CE-FTMS) 进行了分析.

主要成果:

在20分钟内,HTR对PSIL和PME表现出类似的效果.
在治疗后的11天内,PSIL和PME都显著增加了GAP43和synaptophysin在各种大脑区域,PME显示出更广泛的效应.
代谢分析显示,PME和载体组之间存在差异性分离,纯素 (瓜诺辛,素,素) 从载体逐渐下降到PSIL到PME.

结论:

突触蛋白发现表明,PME对突触可塑性具有比PSIL更强大和更长时间的影响.
代谢学数据支持作用梯度 (载体
需要进一步的研究来证实这些发现,并确定负责PME增强效应的分子.

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