Gurgul A, Jasielczuk I, Szmatoła T, Semik-Gurgul E, Kucharski M, Mizera-Szpilka K, Ocłoń E
Faculty of Veterinary Medicine, University of Agriculture in Kraków, Redzina 1 C, 30-248, Krakow, Poland.
Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1, 32-083, Balice, Poland.
J Appl Genet. 2025 May 8. doi: 10.1007/s13353-025-00970-8.
Cannabidiol (CBD) is a compound found in Cannabis sativa that is known for its neuroprotective, anti-inflammatory, analgesic, and anxiolytic properties. These properties make it a promising treatment for various neurological conditions. This study aimed to examine the effects of CBD on hypothalamic neurons at the transcriptome level using the adult-derived mHypoA-2/12 mouse cell line. The cells were exposed to four different CBD concentrations (ranging from 0.325 to 3 µM) for 6 and 24 h. Apart from the transcriptome analysis, apoptosis (caspase 3/7 activity) and viability (MTT) assays were performed. The obtained results showed that CBD enhanced cell viability, especially after 24 h of treatment and at lower or intermediate concentrations, and reduced apoptosis, with significant effects at the highest concentration. CBD caused moderate transcriptome profile changes (13 to 69 genes per treatment), with more genes affected at higher concentrations and shorter exposure times, indicating a stronger initial cellular response. Further analysis revealed that CBD affects several biological processes, including: intrinsic apoptosis suppression via p53 modulation, impacting genes like Bbc3, Mdm2, Cdkn1a, and Smad3. Additionally, CBD influenced genes involved in extracellular matrix organization, including metalloproteinases (Mmp-3, Mmp-13) and their inhibitors (Timp1), as well as collagen components (Col11a1) and mitochondrial respiratory chain complexes (mt-Nd5, mt-Nd4). Genes related to serotonin and dopamine biosynthesis, as well as Aldh2, were also impacted, linking CBD's effects in hypothalamic neurons to potential benefits in managing alcohol use disorders. These findings suggest the hypothalamus is a significant target for CBD, warranting further investigation.
大麻二酚（CBD）是一种在大麻中发现的化合物，以其神经保护、抗炎、镇痛和抗焦虑特性而闻名。这些特性使其成为治疗各种神经系统疾病的有前景的药物。本研究旨在使用成年来源的mHypoA-2/12小鼠细胞系，在转录组水平上研究CBD对下丘脑神经元的影响。将细胞暴露于四种不同浓度的CBD（范围为0.325至3 μM）中6小时和24小时。除了转录组分析外，还进行了凋亡（半胱天冬酶3/7活性）和活力（MTT）测定。获得的结果表明，CBD增强了细胞活力，尤其是在处理24小时后以及在较低或中等浓度下，并且减少了凋亡，在最高浓度下有显著效果。CBD引起了适度的转录组谱变化（每次处理13至69个基因），在较高浓度和较短暴露时间下受影响的基因更多，表明初始细胞反应更强。进一步分析表明，CBD影响了几个生物学过程，包括：通过p53调节抑制内在凋亡，影响Bbc3、Mdm2、Cdkn1a和Smad3等基因。此外，CBD影响了参与细胞外基质组织的基因，包括金属蛋白酶（Mmp-3、Mmp-13）及其抑制剂（Timp1），以及胶原蛋白成分（Col11a1）和线粒体呼吸链复合物（mt-Nd5、mt-Nd4）。与血清素和多巴胺生物合成相关的基因以及Aldh2也受到影响，将CBD在下丘脑神经元中的作用与管理酒精使用障碍的潜在益处联系起来。这些发现表明下丘脑是CBD的重要靶点，值得进一步研究。
