Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13
Cannabidiol, a compound of Cannabis sativa, has been proposed as an alternative treatment of schizophrenia. Preclinical and clinical data have suggested that cannabidiol shares more similarity with atypical antipsychotics than typical, both of which are customarily used to manage schizophrenia sympt...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:af142fd89ab54a98932f445147993b8b2021-12-01T20:21:53ZCannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.131662-509910.3389/fnmol.2021.673144https://doaj.org/article/af142fd89ab54a98932f445147993b8b2021-05-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnmol.2021.673144/fullhttps://doaj.org/toc/1662-5099Cannabidiol, a compound of Cannabis sativa, has been proposed as an alternative treatment of schizophrenia. Preclinical and clinical data have suggested that cannabidiol shares more similarity with atypical antipsychotics than typical, both of which are customarily used to manage schizophrenia symptoms. While oligodendrocytes are known to be relevant targets of antipsychotics, the biochemical knowledge in this regard is still limited. Here we evaluated the molecular pathways modulated by cannabidiol compared to the antipsychotics clozapine (atypical) and haloperidol (typical), additionally evaluating the effects of benztropine, a muscarinic receptor antagonist that displays a protective effect in oligodendrocytes and myelination. For this purpose, we employed nano-chromatography coupled with mass spectrometry to investigate the proteomic response to these drugs both in healthy oligodendrocytic cells and in a cuprizone-based toxicity model, using the human oligodendrocyte precursor cell line MO3.13. Cannabidiol shares similarities of biochemical pathways with clozapine and benztropine, in agreement with other studies that indicated an atypical antipsychotic profile. All drugs tested affected metabolic and gene expression pathways and cannabidiol, benztropine, and clozapine modulated cell proliferation and apoptosis when administered after cuprizone-induced toxicity. These general pathways are associated with cuprizone-induced cytotoxicity in MO3.13 cells, indicating a possible proteomic approach when acting against the toxic effects of cuprizone. In conclusion, although modeling oligodendrocytic cytotoxicity with cuprizone does not represent the entirety of the pathophysiology of oligodendrocyte impairments, these results provide insight into the mechanisms associated with the effects of cannabidiol and antipsychotics against cuprizone toxicity, offering new directions of study for myelin-related processes and deficits.Ana Caroline Brambilla FalvellaBradley Joseph SmithLicia C. Silva-CostaAline G. F. ValençaFernanda CrunfliAntonio W. ZuardiJaime E. HallakJosé A. CrippaValéria de AlmeidaDaniel Martins-de-SouzaDaniel Martins-de-SouzaDaniel Martins-de-SouzaDaniel Martins-de-SouzaFrontiers Media S.A.articlebenztropinehaloperidolclozapineMO3.13 cell linephytocannabinoidproteomeNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Molecular Neuroscience, Vol 14 (2021) |
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benztropine haloperidol clozapine MO3.13 cell line phytocannabinoid proteome Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 |
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benztropine haloperidol clozapine MO3.13 cell line phytocannabinoid proteome Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Ana Caroline Brambilla Falvella Bradley Joseph Smith Licia C. Silva-Costa Aline G. F. Valença Fernanda Crunfli Antonio W. Zuardi Jaime E. Hallak José A. Crippa Valéria de Almeida Daniel Martins-de-Souza Daniel Martins-de-Souza Daniel Martins-de-Souza Daniel Martins-de-Souza Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13 |
| description |
Cannabidiol, a compound of Cannabis sativa, has been proposed as an alternative treatment of schizophrenia. Preclinical and clinical data have suggested that cannabidiol shares more similarity with atypical antipsychotics than typical, both of which are customarily used to manage schizophrenia symptoms. While oligodendrocytes are known to be relevant targets of antipsychotics, the biochemical knowledge in this regard is still limited. Here we evaluated the molecular pathways modulated by cannabidiol compared to the antipsychotics clozapine (atypical) and haloperidol (typical), additionally evaluating the effects of benztropine, a muscarinic receptor antagonist that displays a protective effect in oligodendrocytes and myelination. For this purpose, we employed nano-chromatography coupled with mass spectrometry to investigate the proteomic response to these drugs both in healthy oligodendrocytic cells and in a cuprizone-based toxicity model, using the human oligodendrocyte precursor cell line MO3.13. Cannabidiol shares similarities of biochemical pathways with clozapine and benztropine, in agreement with other studies that indicated an atypical antipsychotic profile. All drugs tested affected metabolic and gene expression pathways and cannabidiol, benztropine, and clozapine modulated cell proliferation and apoptosis when administered after cuprizone-induced toxicity. These general pathways are associated with cuprizone-induced cytotoxicity in MO3.13 cells, indicating a possible proteomic approach when acting against the toxic effects of cuprizone. In conclusion, although modeling oligodendrocytic cytotoxicity with cuprizone does not represent the entirety of the pathophysiology of oligodendrocyte impairments, these results provide insight into the mechanisms associated with the effects of cannabidiol and antipsychotics against cuprizone toxicity, offering new directions of study for myelin-related processes and deficits. |
| format |
article |
| author |
Ana Caroline Brambilla Falvella Bradley Joseph Smith Licia C. Silva-Costa Aline G. F. Valença Fernanda Crunfli Antonio W. Zuardi Jaime E. Hallak José A. Crippa Valéria de Almeida Daniel Martins-de-Souza Daniel Martins-de-Souza Daniel Martins-de-Souza Daniel Martins-de-Souza |
| author_facet |
Ana Caroline Brambilla Falvella Bradley Joseph Smith Licia C. Silva-Costa Aline G. F. Valença Fernanda Crunfli Antonio W. Zuardi Jaime E. Hallak José A. Crippa Valéria de Almeida Daniel Martins-de-Souza Daniel Martins-de-Souza Daniel Martins-de-Souza Daniel Martins-de-Souza |
| author_sort |
Ana Caroline Brambilla Falvella |
| title |
Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13 |
| title_short |
Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13 |
| title_full |
Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13 |
| title_fullStr |
Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13 |
| title_full_unstemmed |
Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13 |
| title_sort |
cannabidiol displays proteomic similarities to antipsychotics in cuprizone-exposed human oligodendrocytic cell line mo3.13 |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/af142fd89ab54a98932f445147993b8b |
| work_keys_str_mv |
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