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Effect of inhibitors of DNMTs and antidepressants on DNA methylation in candidate genes involved in the neurobiology of depression

Grant number: 15/01955-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2016
Effective date (End): March 31, 2018
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Sâmia Regiane Lourenço Joca
Grantee:Amanda Juliana Sales
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Epigenetic mechanisms, such as DNA methylation (is regulated by DNMTs), are thought to play an important role in the neurobiology of depression. In this sense, we demonstrated that inhibitors DNA methylation have antidepressant-like effect in animals submitted to forced swimming test and tail suspension. Objectives: Whereas DNMTs inhibitors have different mechanism of action the conventional antidepressants, this study will test the hypothesis that these drugs induce the same behavioral effect but acute and long term. In addition, we will evaluate if the stress would be able to induce change in the mRNA and DNA methylation levels in different genes associated with depression and regulated by epigenetic mechanisms (BDNF, TrkB, 5-HT1A, NMDA, AMPA) in different brain structures (dorsal and ventral hippocampus, and prefrontal cortex) and whether these changes were attenuated by treatment with acute administration of DNMTs inhibitors and chronis adinistration of antidepressants. Methods: Rats will be submitted to the inescapable shocks (IC) or habituation (Hab) and will receive systemic injection of DNMTs inhibitors, 5-Azad (0.1, 0.2 and 0.4 mg / kg; n=10-12/group) and RG108 (0.2, 0.4 and 0.6 mg / kg; n=10-12/group), antidepressants, imipramine (15 mg / kg; n=10-12/group) or fluoxetine (20 mg / kg; n=10-12/group) or vehicle for 1 (acute group) or 7 days (chronic group) and submitted to the learned helplessness test on the last day. Additionally, a group will be submitted only to the pre-test and will receive the treatments, and the last injection will be administered 1 hour before sacrifice (n=10-12/group). The animals will be anesthetized, decapitated and dissected the brain structures for RNA and methylated DNA isolation for subsequent quantification by real time qPCR.

News published in Agência FAPESP Newsletter about the scholarship:
Scientists seek faster route to treat depression 
Articles published in other media outlets (81 total):
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Folha.com: Cientistas pesquisam caminho mais rápido para tratar depressão com moduladores epigenéticos (21/Dec/2020)
Portal Exame: Cientistas buscam caminho mais rápido para tratar depressão (21/Dec/2020)
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Moneyrf.com: Scientists Seek Faster Route To Treat Depression (18/Jan/2021)
GMS Balaclava: Scientists Seek Faster Route To Treat Depression (18/Jan/2021)
Canal Daqui: Cientistas descobrem caminho para tratar a depressão de maneira mais rápida (17/Jan/2021)
Santé log (França): Dépression : La voie épigénétique pour réparer très vite la neuroplasticité (15/Jan/2021)
Noticias Entre Amigos (República Dominicana): El camino más rápido para tratar la depresión (13/Jan/2021)
Sitios Fuente (México): El camino más rápido para tratar la depresión (12/Jan/2021)
Regenerative Medical Group: Scientists seek faster route to treat depression (12/Jan/2021)
DigestFeed: Scientists seek faster route to treat depression (12/Jan/2021)
Diario Salud (República Dominicana): El camino más rápido para tratar la depresión (11/Jan/2021)
Medindia (Índia): Accelerating Treatment For Depression (09/Jan/2021)
Programa InfoSalud (Argentina): Científicos buscan el camino más rápido para tratar la depresión (08/Jan/2021)
M3 India (Índia): Scientists seek faster route to treat depression (07/Jan/2021)
Pourquoi Docteur (França): L’épigénétique au service du traitement de la dépression (06/Jan/2021)
Health Medicine Network (EUA): Scientists seek faster route to treat depression (05/Jan/2021)
LabRoots (EUA): Promising Epigenetic Treatment for Depression Works After One Dose (05/Jan/2021)
Republish (Índia): Scientists Seek Faster Route To Treat Depression (05/Jan/2021)
Health News Digest (EUA): Scientists Seek Faster Route to Treat Depression (05/Jan/2021)
MDLinx (EUA): Scientists seek faster route to treat depression (05/Jan/2021)
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Global News: Scientists seek faster route to treat depression (05/Jan/2021)
EN24 News: Scientists seek faster route to treat depression (05/Jan/2021)
Nestia (Singapura): Epigenetic modulators have a rapid antidepressant-like effect, study shows (05/Jan/2021)
MediMagazine (Itália): Depressione: come accelerare l’effetto dei farmaci (05/Jan/2021)
Knowledia (França): Scientists Seek Faster Route to Treat Depression (05/Jan/2021)
Queensland Online News (Austrália): Scientists seek faster route to treat depression (05/Jan/2021)
Adelaide Online News (Austrália): Scientists seek faster route to treat depression – EurekAlert (05/Jan/2021)
The Uncover Reality (Índia): Scientists Seek Faster Route To Treat Depression (05/Jan/2021)
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Australian Online News (Austrália): Scientists seek faster route to treat depression – EurekAlert (05/Jan/2021)
Bioon.com (China): 治疗抑郁症的新方法 (Uma nova maneira de tratar a depressão) (05/Jan/2021)
Biloela Online News (Austrália): Scientists seek faster route to treat depression (05/Jan/2021)
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Medlink Neurology (EUA): Scientists Seek Faster Route To Treat Depression (05/Jan/2021)
Lake Macquarie Online News (Austrália): Scientists seek faster route to treat depression (05/Jan/2021)
Brisbane Online News (Austrália): Scientists seek faster route to treat depression (05/Jan/2021)
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News Medical (Austrália): Epigenetic modulators have a rapid antidepressant-like effect, study shows (04/Jan/2021)
Medical Xpress (Reino Unido): Scientists seek faster route to treat depression (04/Jan/2021)
Newswise (EUA): Scientists seek faster route to treat depression (04/Jan/2021)
Bioengineer (Reino Unido): Scientists seek faster route to treat depression (04/Jan/2021)
Science Codex: Scientists seek faster route to treat depression (04/Jan/2021)
Technology Networks (Reino Unido): Flicking Epigenetic Switches May Create Fast-Acting Antidepressants (04/Jan/2021)
Scienmag Science Magazine (Reino Unido): Scientists seek faster route to treat depression (04/Jan/2021)
Brightsurf: Scientists seek faster route to treat depression (04/Jan/2021)
Neuroscience News (EUA): A Faster Route to Treat Depression (04/Jan/2021)
Saense: Cientistas buscam caminho mais rápido para tratar depressão (04/Jan/2021)
Hale Plus Hearty (Nigéria): Scientists Seek Faster Route to Treat Depression (04/Jan/2021)
7thSpace: Scientists seek faster route to treat depression (04/Jan/2021)
Science News Net: Scientists Seek Faster Route to Treat Depression (04/Jan/2021)
Giachino Plastic Surgery: Scientists seek faster route to treat depression (04/Jan/2021)
Burada Biliyorum (Turquia): #Scientists seek faster route to treat depression (04/Jan/2021)
Ethical Editor EUA): Scientists Seek Faster Route to Treat Depression (04/Jan/2021)
God sown Media (Índia): Scientists Seek Faster Route to Treat Depression (04/Jan/2021)
Globe Health News: Epigenetic modulators have a rapid antidepressant-like effect, study shows (04/Jan/2021)
Warta Saya (Malásia): Scientists Seek Faster Route to Treat Depression (04/Jan/2021)
Love Avia for latest news and articles (EUA): Scientists seek faster route to treat depression (04/Jan/2021)
Health Safe Tips: Epigenetic modulators have a fast antidepressant-like impact, learn about displays (04/Jan/2021)
Insider Bulletin: Scientists seek faster route to treat depression (04/Jan/2021)
Wion News: Epigenetic modulators have a rapid antidepressant-like effect, study shows (04/Jan/2021)
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Quora: Scientists seek faster route to treat depression (04/Jan/2021)
Fresher Planet: Scientists seek faster route to treat depression (04/Jan/2021)
Psychreg (Reino Unido): Scientists Seek Faster Route to Treat Depression (03/Jan/2021)
Jornal do Ônibus: Cientistas descobrem caminho para tratar a depressão de maneira mais rápida (28/Dec/2020)
Plantão News (MT): Cientistas buscam caminho mais rápido para tratar depressão (25/Dec/2020)
Casa de Notícias: Cientistas buscam caminho mais rápido para tratar depressão (23/Dec/2020)
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Portal Tucumã: Depressão: Cientistas buscam caminho mais rápido para tratar doença (22/Dec/2020)
Dom Total: Pesquisadores da USP encontram método mais rápido para tratar a depressão (21/Dec/2020)
Opinião (Rio Branco, Acre) online: Cientistas pesquisam caminho mais rápido para tratar depressão com moduladores epigenéticos (21/Dec/2020)
Noticias de Contagem online: Cientistas buscam caminho mais rápido para tratar depressão (19/Dec/2020)
Galileu online: Pesquisadores brasileiros buscam caminho mais rápido para tratar depressão (18/Dec/2020)
Portal da Enfermagem: Cientistas buscam caminho mais rápido para tratar depressão (18/Dec/2020)
Programa InfoSalud (Argentina): Científicos buscan el camino más directo para tratar la depresión (18/Dec/2020)
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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SALES, AMANDA J.; MACIEL, IZAQUE S.; SUAVINHA, ANGELICA C. D. R.; JOCA, SAMIA R. L. Modulation of DNA Methylation and Gene Expression in Rodent Cortical Neuroplasticity Pathways Exerts Rapid Antidepressant-Like Effects. Molecular Neurobiology, v. 58, n. 2, p. 777-794, FEB 2021. Web of Science Citations: 1.
SALES, AMANDA J.; FOGACA, MANOELA V.; SARTIM, ARIANDRA G.; PEREIRA, VITOR S.; WEGENER, GREGERS; GUIMARAES, FRANCISCO S.; JOCA, SAMIA R. L. Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex. Molecular Neurobiology, v. 56, n. 2, p. 1070-1081, FEB 2019. Web of Science Citations: 17.
SALES, AMANDA J.; CRESTANI, CARLOS C.; GUIMARAES, FRANCISCO S.; JOCA, SAMIA R. L. Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 86, p. 255-261, AUG 30 2018. Web of Science Citations: 11.
SARTIM, ARIANDRA G.; SALES, AMANDA J.; GUIMARAES, FRANCISCO S.; JOCA, SAMIA R. L. Hippocampal mammalian target of rapamycin is implicated in stress-coping behavior induced by cannabidiol in the forced swim test. JOURNAL OF PSYCHOPHARMACOLOGY, v. 32, n. 8, p. 922-931, AUG 2018. Web of Science Citations: 3.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.