Histone 3 Trimethylation Patterns are Associated with Resilience or Stress Susceptibility in a Rat Model of Major Depression Disorder

Major Depressive Disorder (MDD) is a severe and multifactorial psychiatric condition. Evidence has shown that environmental factors, such as stress, significantly explain MDD pathophysiology. Studies have hypothesized that changes in histone methylation patterns are involved in impaired glutamatergi...

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Published in:Molecular neurobiology 2024-08, Vol.61 (8), p.5718-5737
Main Authors: Santos, Lucas, Behrens, Luiza, Barbosa, Camila, Tiefensee-Ribeiro, Camila, Rosa-Silva, Helen, Somensi, Nauana, Brum, Pedro Ozorio, Silveira, Alexandre Kleber, Rodrigues, Matheus Scarpatto, de Oliveira, Jade, Gelain, Daniel Pens, Almeida, Roberto F, Moreira, José Cláudio Fonseca
Format: Article
Language:English
Subjects:
Animal models
Biomedical and Life Sciences
Biomedicine
Cell Biology
Doublecortin protein
Environmental factors
Genotype & phenotype
Glial fibrillary acidic protein
Glutamatergic transmission
Histones
Immunoreactivity
Mental depression
Mental disorders
Methylation
Neurobiology
Neurogenesis
Neurology
Neurosciences
Neurotransmission
Pathophysiology
Pattern recognition
Phenotypes
Sucrose
Citations: Items that this one cites
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Summary:Major Depressive Disorder (MDD) is a severe and multifactorial psychiatric condition. Evidence has shown that environmental factors, such as stress, significantly explain MDD pathophysiology. Studies have hypothesized that changes in histone methylation patterns are involved in impaired glutamatergic signaling. Based on this scenario, this study aims to investigate histone 3 involvement in depression susceptibility or resilience in MDD pathophysiology by investigating cellular and molecular parameters related to i) glutamatergic neurotransmission, ii) astrocytic functioning, and iii) neurogenesis. For this, we subjected male Wistar rats to the Chronic Unpredictable Mild Stress (CUMS) model of depression. We propose that by evaluating the sucrose consumption, open field, and object recognition test performance from animals submitted to CUMS, it is possible to predict with high specificity rats with susceptibility to depressive-like phenotype and resilient to the depressive-like phenotype. We also demonstrated, for the first time, that patterns of H3K4me3, H3K9me3, H3K27me3, and H3K36me3 trimethylation are strictly associated with the resilient or susceptible to depressive-like phenotype in a brain-region-specific manner. Additionally, susceptible animals have reduced DCx and GFAP and resilient animals present increase of AQP-4 immunoreactivity. Together, these results provide evidence that H3 trimethylations are related to the development of the resilient or susceptible to depressive-like phenotype, contributing to further advances in the pathophysiology of MDD and the discovery of mechanisms behind resilience.
ISSN:0893-7648
1559-1182
1559-1182
DOI:10.1007/s12035-024-03912-3