The microtubular cytoskeleton of olfactory neurons derived from patients with schizophrenia or with bipolar disorder: Implications for biomarker characterization, neuronal physiology and pharmacological screening

Benítez‐King, Gloria; Valdés-Tovar, Marcela; Trueta, Citlali; Galván-Arrieta, Tania; Argueta, Jesús; Alarcón, Salvador; Lora-Castellanos, A; Solís‐Chagoyán, Héctor

doi:10.1016/j.mcn.2016.01.013

Cited by 21 publications

(17 citation statements)

References 152 publications

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“…Whilst all three studies contain some support for differential cellular Ca 2+ signalling in bipolar disorder, all were based on very small samples, and no specific finding has yet been unequivocally replicated. Completing the results in neuronal-like cells, no differences have been observed in L-type calcium current properties in preliminary studies of olfactory neuronal cells from individuals with bipolar disorder compared with controls [44,49].…”

Section: Qualitative Synthesessupporting

confidence: 57%

Cellular calcium in bipolar disorder: systematic review and meta-analysis

et al. 2019

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Calcium signalling has long been implicated in bipolar disorder, especially by reports of altered intracellular calcium ion concentrations ([Ca 2+ ]). However, the evidence has not been appraised critically. We carried out a systematic review and metaanalysis of studies of cellular calcium indices in bipolar disorder. 2281 records were identified and 117 screened, of which 32 were eligible and 21 were suitable for meta-analyses. The latter each involved up to 642 patients and 404 control subjects. We found that basal free intracellular [Ca 2+ ] is increased in bipolar disorder, both in platelets and in lymphocytes. The effect size is 0.55, with an estimated elevation of 29%. It is observed in medication-free patients. It is present in mania and bipolar depression, but data are equivocal for euthymia. Cells from bipolar disorder individuals also show an enhanced [Ca 2+ ] response to stimulation with 5-HT or thrombin, by an estimated 25%, with an effect size of 0.63. In studies which included other diagnoses, intracellular basal [Ca 2+ ] was higher in bipolar disorder than in unipolar depression, but not significantly different from schizophrenia. Functional parameters of cellular Ca 2+ (e.g. calcium transients), and neuronal [Ca 2+ ], have been much less investigated, and no firm conclusions can be drawn. In summary, there is a robust, medium effect size elevation of basal and stimulated free intracellular [Ca 2+ ] in bipolar disorder. The results suggest altered calcium functioning in the disorder, and encourage further investigations into the underlying mechanisms, and the implications for pathophysiology and therapeutics.

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Section: Qualitative Synthesessupporting

confidence: 57%

Cellular calcium in bipolar disorder: systematic review and meta-analysis

et al. 2019

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“…Samples of the olfactory neuroepithelium (ON) were obtained from subjects during the morning, as previously described [22,29]. Before the nasal exfoliation, all participants were evaluated and instructed not to fast that morning.…”

Section: Nasal Exfoliation and Cell Culturementioning

confidence: 99%

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

et al. 2020

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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.

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“…Thus, the olfactory neuroepithelium (ON) contains pluripotent cells that can proliferate in vitro and differentiate into multiple cell types including neurons and glia [12]. Studies in ON cells of patients suffering from several different types of neuropsychiatric disorders show specific alterations in cellular function [13,14]. Thus, this peripheral tissue can be used as a surrogate of central nervous system (CNS) function [9,15], and may provide relevant information related to the neuropathology observed in different mental illnesses including substance use disorders.…”

Section: Introductionmentioning

confidence: 99%

Cannabis Users Show Enhanced Expression of CB1-5HT2A Receptor Heteromers in Olfactory Neuroepithelium Cells

et al. 2018

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Cannabinoid CB1 receptors (CBR) and serotonergic 2A receptors (5HTR) form heteromers in the brain of mice where they mediate the cognitive deficits produced by delta-9-tetrahydrocannabinol. However, it is still unknown whether the expression of this heterodimer is modulated by chronic cannabis use in humans. In this study, we investigated the expression levels and functionality of CBR-5HTR heteromers in human olfactory neuroepithelium (ON) cells of cannabis users and control subjects, and determined their molecular characteristics through adenylate cyclase and the ERK 1/2 pathway signaling studies. We also assessed whether heteromer expression levels correlated with cannabis consumption and cognitive performance in neuropsychological tests. ON cells from controls and cannabis users expressed neuronal markers such as βIII-tubulin and nestin, displayed similar expression levels of genes related to cellular self-renewal, stem cell differentiation, and generation of neural crest cells, and showed comparable Na currents in patch clamp recordings. Interestingly, CBR-5HTR heteromer expression was significantly increased in cannabis users and positively correlated with the amount of cannabis consumed, and negatively with age of onset of cannabis use. In addition, a negative correlation was found between heteromer expression levels and attention and working memory performance in cannabis users and control subjects. Our findings suggest that cannabis consumption regulates the formation of CBR-5HTR heteromers, and may have a key role in cognitive processing. These heterodimers could be potential new targets to develop treatment alternatives for cognitive impairments.

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The microtubular cytoskeleton of olfactory neurons derived from patients with schizophrenia or with bipolar disorder: Implications for biomarker characterization, neuronal physiology and pharmacological screening

Cited by 21 publications

References 152 publications

Cellular calcium in bipolar disorder: systematic review and meta-analysis

Cellular calcium in bipolar disorder: systematic review and meta-analysis

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

Cannabis Users Show Enhanced Expression of CB1-5HT2A Receptor Heteromers in Olfactory Neuroepithelium Cells

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