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

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.

Olfactory Neuroepithelium Cells from Cannabis Users Display Alterations to the Cytoskeleton and to Markers of Adhesion, Proliferation and Apoptosis

“…Since the cytoskeleton is closely associated with cell membranes, the interaction of cannabis with the lipid bilayer or membrane bound enzyme systems may adversely affect the architecture of the cytoskeleton. In this sense, a recent study using SR-FTIR spectroscopy found that intracellular lipid chains are disordered in ON cells from cannabis users, the membrane displaying an altered lipid composition with a higher rate of membrane lipid renewal and peroxidation, and more proteins with β-sheet structures (Saladrigas-Manjon et al, 2020). Thus, these data strongly support the increased cell size and cytoskeletal alteration in the ON cells of cannabis users.…”

“…In the field of cannabis, we previously showed that ON cells obtained from cannabis users exhibit changes in the cannabinoid CB1 receptor, and in serotonin 2A receptor heteromer expression and function, both of which were associated with cognitive performance (Galindo et al, 2018). Furthermore, the macromolecular profile of ON cells is also altered in cannabis users, these cells displaying a modified lipid composition, as well as an increase in DNA and histone methylation (Saladrigas-Manjon et al, 2020).…”

FTIR Spectroscopy to Reveal Lipid and Protein Changes Induced on Sperm by Capacitation: Bases for an Improvement of Sample Selection in ART

“…Interestingly, the former was considered as a marker of lipidic character of a cellular compartment, while the ratio 2853/2870 cm −1 was linked to the extent of lipid peroxidation or, more in general, to biophysical modifications of lipidic chains composing cellular membranes [ 29 , 30 ]. In particular, the increasing of this ratio has been related to a higher acyl chain unsaturation level [ 31 ].…”

“…The increment of β-sheet in the pellet cells of fraction 3 may be expected since this conformation is a sign of protein aggregation [ 38 ]. Indeed, a high content of β-sheets proteins in cells and tissues and the conversion from an α-helix rich protein population towards a β-sheets-rich one has been previously used as a hallmark of a pathologic status [ 31 ]. In this view, the increase of the β-structures could be correlated to a higher percentage of poor-quality spermatozoa, i.e., low motility and not viable cells.…”

“…As reported extensively in the literature, lipid bands are commonly used to diagnose the presence of a biophysical modification of cell membranes such as lipid peroxidation, modification of lipids chain length, oxidative stress and degree of acyl chain saturation level [ 29 ]. Noteworthy, this ratio has been recently used also to monitor the benefic effect of cannabis in the treatment of schizophrenia, resulting in a minor disruption of lipid composition, in a reduction of lipid peroxidation and in an increased lipid membrane renewal rate [ 31 ].…”