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  Oligodendrocyte gene expression is reduced by and influences effects of chronic social stress in mice

Cathomas, F., Azzinnari, D., Bergamini, G., Sigrist, H., Buerge, M., Hoop, V., et al. (2019). Oligodendrocyte gene expression is reduced by and influences effects of chronic social stress in mice. Genes, Brain and Behavior, 18(1): e12475. doi:10.1111/gbb.12475.

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 Creators:
Cathomas, Flurin, Author
Azzinnari, Damiano, Author
Bergamini, Giorgio, Author
Sigrist, Hannes, Author
Buerge, Michaela, Author
Hoop, Vanessa, Author
Wicki, Benedikt, Author
Goetze, Lea, Author
Soares, Sergio, Author
Kukelova, Diana, Author
Seifritz, Erich, Author
Goebbels, Sandra1, Author           
Nave, Klaus-Armin2, Author           
Ghandour, Said, Author
Seoighe, Cathal, Author
Hildebrandt, Tobias, Author
Leparc, German, Author
Klein, Holger, Author
Stupka, Elia, Author
Hengerer, Bastian, Author
Pryce, Christopher R., Author more..
Affiliations:
1Developmental neurobiology, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society, ou_2173665              
2Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society, ou_2173664              

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 Abstract: Oligodendrocyte gene expression is downregulated in stress-related neuropsychiatric disorders, including depression. In mice, chronic social stress (CSS) leads to depression-relevant changes in brain and emotional behavior, and the present study shows the involvement of oligodendrocytes in this model. In C57BL/6 (BL/6) mice, RNA-sequencing (RNA-Seq) was conducted with prefrontal cortex, amygdala and hippocampus from CSS and controls; a gene enrichment database for neurons, astrocytes and oligodendrocytes was used to identify cell origin of deregulated genes, and cell deconvolution was applied. To assess the potential causal contribution of reduced oligodendrocyte gene expression to CSS effects, mice heterozygous for the oligodendrocyte gene cyclic nucleotide phosphodiesterase (Cnp1) on a BL/6 background were studied; a 2 genotype (wildtype, Cnp1+/−) × 2 environment (control, CSS) design was used to investigate effects on emotional behavior and amygdala microglia. In BL/6 mice, in prefrontal cortex and amygdala tissue comprising gray and white matter, CSS downregulated expression of multiple oligodendroycte genes encoding myelin and myelin-axon-integrity proteins, and cell deconvolution identified a lower proportion of oligodendrocytes in amygdala. Quantification of oligodendrocyte proteins in amygdala gray matter did not yield evidence for reduced translation, suggesting that CSS impacts primarily on white matter oligodendrocytes or the myelin transcriptome. In Cnp1 mice, social interaction was reduced by CSS in Cnp1+/− mice specifically; using ionized calcium-binding adaptor molecule 1 (IBA1) expression, microglia activity was increased additively by Cnp1+/− and CSS in amygdala gray and white matter. This study provides back-translational evidence that oligodendrocyte changes are relevant to the pathophysiology and potentially the treatment of stress-related neuropsychiatric disorders.

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Language(s): eng - English
 Dates: 2018-03-222019-012019
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1111/gbb.12475
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Title: Genes, Brain and Behavior
Source Genre: Journal
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Publ. Info: Oxford : Blackwell Munksgaard
Pages: - Volume / Issue: 18 (1) Sequence Number: e12475 Start / End Page: - Identifier: ISSN: 1601-1848
CoNE: https://pure.mpg.de/cone/journals/resource/111006469467402