Chiricosta Luigi, D'Angiolini Simone, Gugliandolo Agnese, Salamone Stefano, Pollastro Federica, Mazzon Emanuela
IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.
Department of Pharmaceutical Sciences, University of Eastern Piedmont, Largo Donegani 2, 28100 Novara, Italy.
Pharmaceuticals (Basel). 2023 Sep 7;16(9):1268. doi: 10.3390/ph16091268.
Neuronal cell death is a physiological process that, when uncontrollable, leads to neurodegenerative disorders like spinal cord injury (SCI). SCI represents one of the major causes of trauma and disabilities worldwide for which no effective pharmacological intervention exists. Herein, we observed the beneficial effects of Δ-Tetrahydrocannabinol (Δ-THC) during neuronal cell death recovery. We cultured NSC-34 motoneuron cell line performing three different experiments. A traumatic scratch injury was caused in two experiments. One of the scratched was pretreated with Δ-THC to observe the role of the cannabinoid following the trauma. An experimental control group was neither scratched nor pretreated. All the experiments underwent RNA-seq analysis. The effects of traumatic injury were observed in scratch against control comparison. Comparison of scratch models with or without pretreatment highlighted how Δ-THC counteracts the traumatic event. Our results shown that Δ-THC triggers the cytoskeletal remodeling probably due to the activation of the Janus Kinase Signal Transducer and Activator of Transcription (JAK/STAT) signaling pathway and the signaling cascade operated by the Mitogen-Activated Protein (MAP) Kinase signaling pathway. In light of this evidence, Δ-THC could be a valid pharmacological approach in the treatment of abnormal neuronal cell death occurring in motoneuron cells.
神经元细胞死亡是一个生理过程，当这个过程无法控制时，会导致诸如脊髓损伤（SCI）等神经退行性疾病。脊髓损伤是全球创伤和残疾的主要原因之一，目前尚无有效的药物干预措施。在此，我们观察了Δ-四氢大麻酚（Δ-THC）在神经元细胞死亡恢复过程中的有益作用。我们培养了NSC-34运动神经元细胞系，并进行了三个不同的实验。在两个实验中造成了创伤性划痕损伤。其中一个划痕组用Δ-THC进行预处理，以观察大麻素在创伤后的作用。一个实验对照组既没有划痕也没有预处理。所有实验都进行了RNA测序分析。通过划痕组与对照组的比较观察创伤性损伤的影响。有或没有预处理的划痕模型的比较突出了Δ-THC如何对抗创伤事件。我们的结果表明，Δ-THC可能通过激活 Janus 激酶信号转导子和转录激活子（JAK/STAT）信号通路以及丝裂原活化蛋白（MAP）激酶信号通路所操作的信号级联反应来触发细胞骨架重塑。鉴于这一证据，Δ-THC可能是治疗运动神经元细胞中发生的异常神经元细胞死亡的一种有效药理学方法。
