Will Cannabigerol trigger neuroregeneration after a spinal cord injury? An in vitro answer from NSC-34 scratch-injured cells transcriptome

Spinal cord injury affects the lives of millions of people around the world, often causing disability and, in unfortunate circumstances, death. Rehabilitation can partly improve outcomes and only a small percentage of patients, typically the least injured, can hope to return to normal living conditions. Cannabis Sativa is gaining more and more interest in recent years, even though its beneficial properties have been known for thousands of years. Cannabigerol (CBG), extracted from C. Sativa, is defined as the "mother of all cannabinoids" and its properties range from anti-inflammatory to antioxidant and neuroprotection. Using NSC-34 cells to model spinal cord injury in vitro, our work evaluated the properties of CBG treatments in motorneurons regeneration. While pre-treatment can modulate oxidative stress, increasing antioxidant enzyme genes like Tnx1, decreasing on the other hand Nos1, post-treatment seems able to induce regeneration genes by triggering different pathways, like Gap43 via p53 acetylation by Ep300 and Ddit3 and Xbp1 via Bdnf signaling, along with cytoskeletal remodeling signaling genes Nrp1 and Map1b. Our results indicate CBG as a phytocompound worth to further investigations in the field of neuronal regeneration.

脊髓损伤（Spinal cord injury）影响全球数百万人群的生活，常导致残疾，严重时甚至引发死亡。康复干预仅能部分改善预后，仅少数损伤程度较轻的患者有望恢复正常生活状态。尽管大麻（Cannabis Sativa）的有益特性已被认知数千年，但近年来其研究关注度正持续提升。从大麻中提取的大麻萜酚（Cannabigerol, CBG）被称为"所有大麻素之母"，其活性涵盖抗炎、抗氧化及神经保护等多个领域。本研究利用NSC-34细胞构建体外脊髓损伤模型，评估了CBG干预对运动神经元再生的调控作用。研究发现，CBG预处理可调节氧化应激状态：上调Tnx1等抗氧化酶基因的表达，同时下调Nos1的转录；而CBG后处理则可通过激活多条通路诱导再生相关基因的表达，例如经由Ep300介导的p53乙酰化通路上调Gap43与Ddit3，通过脑源性神经营养因子（Bdnf）信号通路调控Xbp1，同时还可调节细胞骨架重塑相关信号基因Nrp1与Map1b的表达。本研究结果表明，CBG作为一种植物源性活性成分，在神经再生领域具备进一步深入研究的重要价值。