Psychedelics Recruit Multiple Cellular Types and Produce Complex Transcriptional Responses Within the Brain.
Psychedelics Recruit Multiple Cellular Types and Produce Complex Transcriptional Responses Within the Brain.
复制标题
DOI：
10.1016/j.ebiom.2016.08.049
复制
发表时间：
2016-09
期刊：
影响因子：
11.1
通讯作者：
Nichols, Charles D.
中科院分区：
文献类型：
--
作者：
Martin, David A.;Nichols, Charles D.
关键词：
There has recently been a resurgence of interest in psychedelics, substances that profoundly alter perception and cognition and have recently demonstrated therapeutic efficacy to treat anxiety, depression, and addiction in the clinic. The receptor mechanisms that drive their molecular and behavioral effects involve activation of cortical serotonin 5-HT2A receptors, but the responses of specific cellular populations remain unknown. Here, we provide evidence that a small subset of 5-HT2A-expressing excitatory neurons is directly activated by psychedelics and subsequently recruits other select cell types including subpopulations of inhibitory somatostatin and parvalbumin GABAergic interneurons, as well as astrocytes, to produce distinct and regional responses. To gather data regarding the response of specific neuronal populations, we developed methodology for fluorescence-activated cell sorting (FACS) to segregate and enrich specific cellular subtypes in the brain. These methods allow for robust neuronal sorting based on cytoplasmic epitopes followed by downstream nucleic acid analysis, expanding the utility of FACS in neuroscience research. Psychedelics activate distinct transcription across cell types, including excitatory neurons, inhibitory neurons, and astrocytes Psychedelics induce internalization of 5-HT2A receptors throughout the cortex and claustrum FACS can separate neuronal subpopulations that require non-nuclear markers Psychedelic drugs are known to act through the 5-HT2A receptor to produce many of their effects, however, the precise cellular populations in the brain which respond to this class of drugs remain unknown. We use flow cytometric analyses, immunohistochemistry, and gene expression analyses to identify small populations of specific cells in the brain that are activated by the psychedelic drug, (R)-DOI. The methodology used in these studies will be useful to determine the molecular effects of any manipulation or disease on particular brain cells.
登录
查看更多内容
DOI：
10.1177/0269881114548296
发表时间：
2014-11
期刊：
Journal of psychopharmacology (Oxford, England)
影响因子：
--
作者：
Johnson MW;Garcia-Romeu A;Cosimano MP;Griffiths RR
通讯作者：
Griffiths RR
影响因子：
7.6
作者：
Abi-Saab, WM;Bubser, M;Deutch, AY
通讯作者：
Deutch, AY
DOI：
10.1074/mcp.m113.036558
发表时间：
2014-05
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Karaki S;Becamel C;Murat S;Mannoury la Cour C;Millan MJ;Prézeau L;Bockaert J;Marin P;Vandermoere F
通讯作者：
Vandermoere F
影响因子：
4.7
作者：
Liu, Qing-Rong;Rubio, Francisco J.;Hope, Bruce T.
通讯作者：
Hope, Bruce T.
影响因子：
6.1
作者：
GLENNON, RA;TITELER, M;MCKENNEY, JD
通讯作者：
MCKENNEY, JD