Integrative Pharmacology and Systems Neuroscience, IMIM-Hospital del Mar Research Institute, 08003 Barcelona, Spain.
ALBA-CELLS Synchrotron, MIRAS Beamline, 08290 Cerdanyola del Vallès, Spain.
Biomolecules. 2020 Feb 19;10(2):329. doi: 10.3390/biom10020329.
Schizophrenia (SCZ) is a neurodevelopmental disorder with a high genetic component, but the presence of environmental stressors can be important for its onset and progression. Cannabis use can be a major risk factor for developing SCZ. However, despite the available data on the neurobiological underpinnings of SCZ, there is an important lack of studies in human neuronal tissue and living cells addressing the effects of cannabis in SCZ patients. In this study, we analysed the most relevant bio-macromolecular constituents in olfactory neuroepithelium (ON) cells of healthy controls non-cannabis users, healthy cannabis users, SCZ patients non-cannabis users, and SCZ patients cannabis users using Synchrotron Radiation-Fourier Transform Infrared (SR-FTIR) spectrometry and microscopy. Our results revealed that SCZ patients non-cannabis users, and healthy cannabis users exhibit similar alterations in the macromolecular profile of ON cells, including disruption in lipid composition, increased lipid membrane renewal rate and lipid peroxidation, altered proteins containing more β-sheet structures, and showed an increase in DNA and histone methylation. Notably, these alterations were not observed in SCZ patients who use cannabis regularly. These data suggest a differential effect of cannabis in healthy controls and in SCZ patients in terms of the macromolecular constituents of ON cells.
精神分裂症 (SCZ) 是一种具有高度遗传成分的神经发育障碍，但环境应激因素的存在可能对其发病和进展很重要。大麻的使用可能是导致 SCZ 的一个主要危险因素。然而，尽管有关于 SCZ 神经生物学基础的可用数据，但在人类神经元组织和活细胞中，针对 SCZ 患者中大麻影响的研究仍然严重缺乏。在这项研究中，我们使用同步辐射-傅里叶变换红外（SR-FTIR）光谱和显微镜分析了健康对照组非大麻使用者、健康大麻使用者、SCZ 患者非大麻使用者和 SCZ 患者大麻使用者的嗅神经上皮 (ON) 细胞中最相关的生物大分子成分。我们的结果表明，SCZ 患者非大麻使用者和健康大麻使用者的 ON 细胞的大分子谱表现出相似的改变，包括脂质组成的破坏、脂质膜更新率的增加和脂质过氧化、含有更多β-折叠结构的蛋白质改变，以及 DNA 和组蛋白甲基化增加。值得注意的是，在经常使用大麻的 SCZ 患者中没有观察到这些改变。这些数据表明，大麻对健康对照组和 SCZ 患者的 ON 细胞的大分子成分有不同的影响。
