CBD modulates DNA methylation in the prefrontal cortex and hippocampus of mice exposed to forced swim
Abstract
Cannabidiol (CBD), a non-psychotomimetic component of Cannabis sativa plant, shows therapeutic potential in psychiatric disorders, including depression. The molecular mechanisms underlying the antidepressant-like effects of CBD are not yet understood. Previous studies in differentiated skin cells demonstrated that CBD regulates DNA methylation, an overall repressive epigenetic mechanism. Both stress exposure and antidepressant treatment can modulate DNA methylation in the brain, and lead to gene expression changes associated with depression neurobiology. We investigated herein if the antidepressant effect of CBD could be associated with changes in DNA methylation in the prefrontal cortex (PFC) and hippocampus (HPC) of mice submitted to the forced swimming test (FST). Therefore, we assessed: i) the behavioral effects induced by CBD and DNA methylation inhibitors (DNMTi: 5-AzaD and RG108), alone or in association; ii) the effects induced by CBD and DNMTi in global DNA methylation and DNMT activity, in PFC and HPC. Results showed that treatment with CBD (10 mg/kg), 5-AzaD and RG108 (0.2 mg/kg) induced an antidepressant-like effect in the FST. Similar effects were observed after the combination of sub-effective doses of CBD (7 mg/kg) and 5-AzaD or CBD (7 mg/kg) and RG108 (0.1 mg/kg). Also, stress reduced DNA methylation and DNMT activity in the HPC and increased it in the PFC. CBD and DNMTi treatment prevented these changes in both brain structures. Altogether, our results indica…
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CBD administration prevented stress-induced epigenetic changes in both the hippocampus and PFC.
“Interestingly, CBD administration prevented stress-induced epigenetic changes in both the hippocampus and PFC.397”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [397]
Stress induced by FST increased levels of global DNA methylation levels and DNMT activity in the hippocampus while decreasing DNA methylation and DNMT activity in the prefrontal cortex.
“In one study,397 stress induced by FST increased levels of global DNA methylation levels and DNMT activity in the hippocampus while decreasing DNA methylation and DNMT activity in the prefrontal cortex.”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [397]
Cites
Assessing antidepressant activity in rodents: recent developments and future needs
Cryan, J. F., Markou, A., & Lucki, I. (2002) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(02)02017-5 · Cited by 1,551 · see citing works
Cannabidiol is a negative allosteric modulator of the cannabinoid CB <sub>1</sub> receptor
Laprairie, R. B., Bagher, A. M., Kelly, M. E. M., & Denovan‐Wright, E. M. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13250 · Cited by 1,039 · see citing works
The role of 5-HT receptors in depression
Yohn, C. N., Gergues, M. M., & Samuels, B. A. (2017) · Molecular Brain · doi:10.1186/s13041-017-0306-y · Cited by 485 · see citing works
Esposito, G., Scuderi, C., Valenza, M., Togna, G. I., Latina, V., De Filippis, D., Cipriano, M., Carratù, M. R., Iuvone, T., & Steardo, L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028668 · Cited by 410 · see citing works
Progress in Epigenetics of Depression
Peña, C. J., & Nestler, E. J. (2018) · Progress in Molecular Biology and Translational Science · doi:10.1016/bs.pmbts.2017.12.011 · Cited by 84 · see citing works
Epigenetic Regulation of BDNF Gene during Development and Diseases
Chen, K.-W., & Chen, L. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18030571 · Cited by 75 · see citing works
Sales, A. J., & Joca, S. R. L. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.01.022 · Cited by 47 · see citing works
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García-Gutiérrez, M. S., Navarrete, F., Gasparyan, A., Austrich-Olivares, A., Sala, F., & Manzanares, J. (2020) · Biomolecules · doi:10.3390/biom10111575 · Cited by 306 · see citing works
Yuan, M., Yang, B., Rothschild, G., Mann, J. J., Sanford, L. D., Tang, X., Huang, C., Wang, C., & Zhang, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01519-z · Cited by 246 · see citing works
“Interestingly, CBD administration prevented stress-induced epigenetic changes in both the hippocampus and PFC. 397 A preliminary study reported that several histone modi fi cations were changed in some brain regions of rats after CBD administration.”
Background
- Authors
- Sales, A. J., Guimarães, F. S., & Joca, S. R. L.
- Affiliations
- Universidade de São Paulo (BR)
- Corresponding author
- Joca, Sâmia R.L.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2020-06
- Volume
- 388
- Pages
- 112627
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W3020345240
- Cited by
- 58
- References
- 7
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 11 · 2023: 17 · 2022: 10 · 2021: 8 · 2020: 3
- FWCI
- 5.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Scopus (Elsevier) (submittedVersion)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- cannabidiol, DNA methylation, depression, antidepressant-like effects, forced swim test, prefrontal cortex, hippocampus, hypomethylating agents, decitabine, RG108, epigenetics, stress
- MeSH terms
- Animals, Antidepressive Agents, Cannabidiol, Depression, Disease Models, Animal, Hippocampus, Male, Prefrontal Cortex, DNA Methylation, Epigenesis, Genetic, Mice
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