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在炎性条件下小胶质细胞中 CB2 的表达：从图谱到调控。

CB2 expression in mouse brain: from mapping to regulation in microglia under inflammatory conditions.

机构信息

CNRS UMR5292, Inserm U1028, TIGER Team, Université Claude Bernard Lyon 1, Centre de Recherche en Neurosciences de Lyon, 69500, Bron, France.

Epilepsy Institute IDEE, 59 Boulevard Pinel, 69500, Bron, France.

出版信息

J Neuroinflammation. 2024 Aug 19;21(1):206. doi: 10.1186/s12974-024-03202-8.

DOI:10.1186/s12974-024-03202-8
PMID:39160534
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11334370/
Abstract

Since its detection in the brain, the cannabinoid receptor type 2 (CB2) has been considered a promising therapeutic target for various neurological and psychiatric disorders. However, precise brain mapping of its expression is still lacking. Using magnetic cell sorting, calibrated RT-qPCR and single-nucleus RNAseq, we show that CB2 is expressed at a low level in all brain regions studied, mainly by few microglial cells, and by neurons in an even lower proportion. Upon lipopolysaccharide stimulation, modeling neuroinflammation in non-sterile conditions, we demonstrate that the inflammatory response is associated with a transient reduction in CB2 mRNA levels in brain tissue, particularly in microglial cells. This result, confirmed in the BV2 microglial cell line, contrasts with the positive correlation observed between CB2 mRNA levels and the inflammatory response upon stimulation by interferon-gamma, modeling neuroinflammation in sterile condition. Discrete brain CB2 expression might thus be up- or down-regulated depending on the inflammatory context.

摘要

自从在大脑中检测到大麻素受体 2 (CB2) 以来，它一直被认为是治疗各种神经和精神疾病的有希望的治疗靶点。然而，其表达的精确脑图谱仍然缺乏。使用磁性细胞分选、校准的 RT-qPCR 和单核 RNAseq，我们表明 CB2 在所有研究的脑区均以低水平表达，主要由少数小胶质细胞表达，神经元的表达比例更低。在脂多糖刺激下，模拟非无菌条件下的神经炎症，我们证明炎症反应与脑组织中 CB2 mRNA 水平的短暂降低有关，特别是在小胶质细胞中。这一结果在 BV2 小胶质细胞系中得到了证实，与在无菌条件下用干扰素-γ刺激模拟神经炎症时观察到的 CB2 mRNA 水平与炎症反应之间的正相关形成对比。因此，根据炎症的情况，大脑中 CB2 的表达可能会增加或减少。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fbf/11334370/6dbe055824a6/12974_2024_3202_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fbf/11334370/08e74feef77e/12974_2024_3202_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fbf/11334370/01393a1db87c/12974_2024_3202_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fbf/11334370/93163d89c01a/12974_2024_3202_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fbf/11334370/d243db85d67b/12974_2024_3202_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fbf/11334370/3ac9894ba27e/12974_2024_3202_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fbf/11334370/6dbe055824a6/12974_2024_3202_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fbf/11334370/08e74feef77e/12974_2024_3202_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fbf/11334370/42fe44f1bdba/12974_2024_3202_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fbf/11334370/01393a1db87c/12974_2024_3202_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fbf/11334370/93163d89c01a/12974_2024_3202_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fbf/11334370/d243db85d67b/12974_2024_3202_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fbf/11334370/3ac9894ba27e/12974_2024_3202_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fbf/11334370/6dbe055824a6/12974_2024_3202_Fig7_HTML.jpg

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