特定合成大麻素对神经元衰老的潜在影响：对SH-SY5Y细胞增殖和β -半乳糖苷酶活性的影响

Emerging trends in drugs, addictions, and health Pub Date : 2024-12-01 DOI:10.1016/j.etdah.2023.100118

R. Roque-Bravo, H. Carmo, J. Pedro Silva, F. Carvalho, D. Dias da Silva

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引用次数: 0

摘要

合成大麻素（SC）的药理机制与大麻的主要活性成分Δ9-tetrahydrocannabinol （THC）相似。与四氢大麻酚的部分激动作用相比，SC是对CB1和CB2受体具有更高效力的完全激动剂。大麻的使用加速了衰老的某些方面，所以SC的作用似乎是相似的。因此，本研究确定了SC暴露对体外神经元细胞增殖和β -半乳糖苷酶活性（衰老标志）的影响，以研究其可能的促衰老作用。方法将人神经母细胞瘤SH-SY5Y细胞分别暴露于1µM、1nM和1pM的AMB-FUBINACA和ADB-FUBINACA中24、48、72和96h，然后进行硫磺胺B测定（间接测量细胞增殖）。为了确定CB1R和CB2R的作用，在选择性拮抗剂SR141716A和SR144528存在0.5µM的条件下，细胞预孵育20分钟后重复实验。使用Enzo生命科学细胞分离活性测定试剂盒，在1µM和1nM AMB-FUBINACA中暴露22代（P24-46, 68天）的细胞中测量β -半乳糖苷酶活性。结果96h时，SH-SY5Y细胞在两种SC浓度下增殖均增强（p < 0.05）；CB1拮抗剂可逆转AMB-FUBINACA的增殖，而CB2拮抗剂可逆转两种SC的增殖作用（p<0.05）。初步结果显示sc处理的细胞在传代46时β -半乳糖苷酶活性增加（p<0.05）。这些结果表明SC可能对衰老相关标志物产生影响，证明需要测试其他神经元衰老标志物。

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Potential Effects of Selected Synthetic Cannabinoids on Neuronal Senescence: Impact on Proliferation and Beta-Galactosidase Activity in SH-SY5Y Cells

Introduction

Synthetic cannabinoids (SC) display a pharmacological mechanism similar to that of Δ9-tetrahydrocannabinol (THC), the key active principle of cannabis. SC are full agonists with higher potency at the CB1 and CB2 receptors, contrasting with THC's partial agonism. Cannabis use precipitates certain aspects of senescence/ageing, so it is plausible that SC act alike. Thus, for the present study the impact of SC exposure on in vitro neuronal cells proliferation and beta-galactosidase activity (a marker of senescence) was determined, to investigate their putative pro-senescence effects.

Methods

Human neuroblastoma SH-SY5Y cells were exposed to 1µM, 1nM and 1pM AMB-FUBINACA and ADB-FUBINACA for 24, 48, 72 and 96h, after which the sulforhodamine B assay (an indirect measure of cell proliferation) was conducted. To determine CB1R and CB2R involvement, the assays were repeated after cells’ pre-incubation for 20 min in the presence of the selective antagonists, SR141716A and SR144528, respectively, at 0.5µM. Beta-galactosidase activity was measured in cells exposed to 1µM and 1nM AMB-FUBINACA for 22 passages (P24-46, 68 days), using the Enzo Life Sciences Cellular Secescence Activity Assay kit.

Results

At 96h, SH-SY5Y proliferation was increased after exposure to test concentrations of both SC (p<0.05); the use of CB1 antagonist reverted proliferation for AMB-FUBINACA, while CB2 antagonist reversed effects for both SC (p<0.05). Preliminary results show increased beta-galactosidase activity at passage 46 in SC-treated cells (p<0.05).

Conclusions

These results show a possible influence of SC on senescence-associated markers, proving the need to test additional neuronal ageing markers.

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来源期刊

Emerging trends in drugs, addictions, and health Pharmacology, Psychiatry and Mental Health, Forensic Medicine, Drug Discovery, Pharmacology, Toxicology and Pharmaceutics (General)

CiteScore

2.40

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0.00%

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