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. 2020 Feb 19;10(2):329.
doi: 10.3390/biom10020329.

Effects of Cannabis Use on the Protein and Lipid Profile of Olfactory Neuroepithelium Cells From Schizophrenia Patients Studied by Synchrotron-Based FTIR Spectroscopy

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Effects of Cannabis Use on the Protein and Lipid Profile of Olfactory Neuroepithelium Cells From Schizophrenia Patients Studied by Synchrotron-Based FTIR Spectroscopy

Sergi Saladrigas-Manjón et al. Biomolecules. .
Free PMC article

Abstract

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.

Keywords: SR-FTIR; cannabis; olfactory neuroepithelium; schizophrenia.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mean FTIR of dried olfactory neuroepithelium (ON) cells from healthy controls non-cannabis users (HC/nc, green); healthy controls cannabis users (HC/c, light blue); schizophrenic patients non-cannabis users (SCZ/nc, dark blue) and schizophrenic patients cannabis users (SCZ/c, red). The main peaks are assigned for (A) the lipid region (3050–2800 cm−1), and (B) the protein fingerprint region (1800–900 cm−1). Contribution of the first two components in the principal component analysis (PCA) for lipids (3050–2800 cm−1) (C,D), and for proteins (1800–1480 cm−1) (E,F). In C, and E, symbols represent the mean values for each subject.
Figure 2
Figure 2
Major peak amplitudes related to the CH2 (A) 2923 cm-1, (B) 2852 cm-1 and (C) the ratio between 2852/2871 cm-1 in ON cells from healthy controls non-cannabis users (HC/nc); healthy controls cannabis users (HC/c); schizophrenic patients non-cannabis users (SCZ/nc) and schizophrenic patients cannabis users (SCZ/c). The data are expressed as means ± S.E.M. *p < 0.05; **p < 0.01; ***p < 0.001 vs. HC/nc. !p < 0.05; !!p < 0.01; !!!p < 0.001 HC/c vs. SCZ/nc. #p < 0.05; ##p < 0.01; ###p < 0.001 SCZ/nc vs. SCZ/c.
Figure 3
Figure 3
Major peak amplitudes related to the CH3 (A) 2956 cm−1, (B) 2871 cm−1, (C) the cholesteryl esters 1168 cm−1 and (D) the aromatic cys-alkelene (HC=CH) group 3016 cm−1 in ON cells from healthy controls non-cannabis users (HC/nc); healthy controls cannabis users (HC/c); schizophrenic patients non-cannabis users (SCZ/nc) and schizophrenic patients cannabis users (SCZ/c). The data are expressed as means ± S.E.M. * p < 0.05; ** p < 0.01; *** p < 0.001 vs. HC/nc. ! p < 0.05; !! p < 0.01; !!! p < 0.001 HC/c vs. SCZ/nc. # p < 0.05; ## p < 0.01; ### p < 0.001 SCZ/nc vs. SCZ/c.
Figure 4
Figure 4
Peak amplitudes for the methylation related peak 2936 cm-1 (A) and the symmetric stretching vibrations of the phosphate group (1081 cm-1) (B) in ON cells from healthy controls non-cannabis users (HC/nc); healthy controls cannabis users (HC/c); schizophrenic patients non-cannabis users (SCZ/nc) and schizophrenic patients cannabis users (SCZ/c). The data are expressed as means ± S.E.M. * p < 0.05; ** p < 0.01; *** p < 0.001 vs. HC/nc. ! p < 0.05; !! p < 0.01; !!! p < 0.001 HC/c vs. SCZ/nc. # p < 0.05; ## p < 0.01; ### p < 0.001 SCZ/nc vs. SCZ/c.
Figure 5
Figure 5
Major peak amplitudes related to the protein signature in ON cells from healthy controls non-cannabis users (HC/nc); healthy controls cannabis users (HC/c); schizophrenic patients non-cannabis users (SCZ/nc) and schizophrenic patients cannabis users (SCZ/c). (A) Peak amplitudes for the Amide I peak (1652 cm−1). (B,C) Amide I area FTIR spectra deconvolution expressed as the percentage of the integrated area (%) of the protein secondary structures related to their centred peak positions. (B) Side chains/cross β-sheet (1616 cm−1), and antiparallel β-sheet (1690 cm−1). (C) β-sheet/unordered (1634 cm−1), α-helix (1655 cm−1), and turns & loops (1679 cm−1). The data are expressed as means ± S.E.M. * p < 0.05; ** p < 0.01; *** p < 0.001 vs. HC/nc. ! p < 0.05; !! p < 0.01; !!! p < 0.001 HC/c vs. SCZ/nc.

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