Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Italy.
Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
J Neurochem. 2022 Jul;162(1):9-23. doi: 10.1111/jnc.15534. Epub 2021 Nov 14.
Psychedelic drugs are gaining attention from the scientific community as potential new compounds for the treatment of psychiatric diseases such as mood and substance use disorders. The 5-HT receptor has been identified as the main molecular target, and early studies pointed to an effect on the expression of neuroplasticity genes. Analysing RNA-seq data from the prefrontal cortex of rats chronically treated with lysergic acid diethylamide (LSD), we describe the psychedelic-induced rewiring of gene co-expression networks, which become less centralised but more complex, with an overall increase in signalling entropy typical of highly plastic systems. Intriguingly, signalling entropy mirrors, at the molecular level, the increased brain entropy reported through neuroimaging studies in human, suggesting the underlying mechanisms of higher-order phenomena. Moreover, from the analysis of network topology, we identify potential transcriptional regulators and propose the involvement of different cell types in psychedelics' activity.
迷幻药物作为治疗情绪和物质使用障碍等精神疾病的潜在新化合物，正引起科学界的关注。5-HT 受体已被确定为主要的分子靶点，早期研究表明其对神经可塑性基因表达有影响。通过对慢性给予麦角酸二乙酰胺（LSD）的大鼠前额叶皮质的 RNA-seq 数据分析，我们描述了迷幻药引起的基因共表达网络重布线，这些网络变得不那么集中但更复杂，整体信号熵增加，这是高度可塑性系统的典型特征。有趣的是，信号熵在分子水平上反映了神经影像学研究在人类中报告的大脑熵的增加，这表明存在更高阶现象的潜在机制。此外，通过网络拓扑分析，我们确定了潜在的转录调节剂，并提出了不同细胞类型在迷幻药作用中的参与。
