Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941902, Brazil.
Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941902, Brazil.
Int J Mol Sci. 2023 Jul 21;24(14):11775. doi: 10.3390/ijms241411775.
The endocannabinoid system (eCS) is widely distributed in mammalian tissues and it is classically formed by cannabinoid receptors, endogenous bioactive lipids and its synthesis and degradation enzymes. Due to the modulatory role of eCS in synaptic activity in the Central Nervous System (CNS), phytocannabinoids have been increasingly used for the treatment of neurological disorders, even though little is known in terms of the long-term effect of these treatments on CNS development, mainly in the timeframe that comprises childhood and adolescence. Furthermore, an increased number of clinical trials using full-spectrum extracts has been seen, rather than the isolated form of phytocannabinoids, when exploring the therapeutical benefits of the plant. Thus, this study aims to evaluate the effect of cannabidiol (CBD)-enriched extract on synaptic components in the hippocampus of rats from adolescence to early adulthood (postnatal day 45 to 60). Oral treatment of healthy male Wistar rats with a CBD-enriched extract (3 mg/kg/day CBD) during 15 days did not affect food intake and water balance. There was also no negative impact on locomotor behaviour and cognitive performance. However, the hippocampal protein levels of GluA1 and GFAP were reduced in animals treated with the extract, whilst PSD95 levels were increased, which suggests rearrangement of glutamatergic synapses and modulation of astrocytic features. Microglial complexity was reduced in CA1 and CA3 regions, but no alterations in their phagocytic activity have been identified by Iba-1 and LAMP2 co-localization. Collectively, our data suggest that CBD-enriched treatment may be safe and well-tolerated in healthy subjects, besides acting as a neuroprotective agent against hippocampal alterations related to the pathogenesis of excitatory and astrogliosis-mediated disorders in CNS.
内源性大麻素系统（eCS）广泛分布于哺乳动物组织中，经典地由大麻素受体、内源性生物活性脂质及其合成和降解酶组成。由于 eCS 在中枢神经系统（CNS）突触活动中的调节作用，植物大麻素已被越来越多地用于治疗神经紊乱，尽管对于这些治疗方法对 CNS 发育的长期影响知之甚少，主要是在包括儿童和青少年时期的时间段内。此外，当探索植物的治疗益处时，越来越多的临床试验使用全谱提取物，而不是植物大麻素的分离形式。因此，本研究旨在评估大麻二酚（CBD）富集提取物对青春期至成年早期（出生后第 45 天至 60 天）大鼠海马突触成分的影响。15 天内用 CBD 富集提取物（3 mg/kg/天 CBD）对健康雄性 Wistar 大鼠进行口服治疗，不会影响食物摄入和水平衡。运动行为和认知表现也没有受到负面影响。然而，用提取物处理的动物海马中 GluA1 和 GFAP 的蛋白水平降低，而 PSD95 水平升高，这表明谷氨酸能突触的重排和星形胶质细胞特征的调节。CA1 和 CA3 区的小胶质细胞复杂性降低，但通过 Iba-1 和 LAMP2 共定位未发现其吞噬活性的改变。总的来说，我们的数据表明，CBD 富集治疗在健康受试者中可能是安全且耐受良好的，并且可以作为神经保护剂，对抗与中枢神经系统兴奋性和星形胶质细胞介导的疾病发病机制相关的海马改变。
