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Cathomas, F., Azzinnari, D., Bergamini, G., Sigrist, H., Buerge, M., Hoop, V., Wicki, B., Goetze, L., Soares, S. M. P., Kukelova, D., Seifritz, E., Goebbels, S., Nave, K.-A., Ghandour, M. S., Seoighe, C., Hildebrandt, T., Leparc, G., Klein, H., Stupka, E., Hengerer, B. and 1 moreCathomas, F., Azzinnari, D., Bergamini, G., Sigrist, H., Buerge, M., Hoop, V., Wicki, B., Goetze, L., Soares, S. M. P., Kukelova, D., Seifritz, E., Goebbels, S., Nave, K.-A., Ghandour, M. S., Seoighe, C., Hildebrandt, T., Leparc, G., Klein, H., Stupka, E., Hengerer, B., & Pryce, C. R. (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.
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. -
Soares, S. M. P., Ong, G., Abutalebi, J., Del Maschio, N., Sewell, D., & Weekes, B. (2019). A diffusion model approach to analyzing performance on the flanker task: the role of the DLPFC. Bilingualism: Language and Cognition, 22(5), 1194-1208. doi:10.1017/S1366728918000974.
Abstract
The anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC) are involved in conflict detection and
conflict resolution, respectively. Here, we investigate how lifelong bilingualism induces neuroplasticity to these structures by
employing a novel analysis of behavioural performance. We correlated grey matter volume (GMV) in seniors reported by
Abutalebi et al. (2015) with behavioral Flanker task performance fitted using the diffusion model (Ratcliff, 1978). As
predicted, we observed significant correlations between GMV in the DLPFC and Flanker performance. However, for
monolinguals the non-decision time parameter was significantly correlated with GMV in the left DLPFC, whereas for
bilinguals the correlation was significant in the right DLPFC. We also found a significant correlation between age and GMV
in left DLPFC and the non-decision time parameter for the conflict effect for monolinguals only.
We submit that this is due to cumulative demands on cognitive control over a lifetime of bilingual language processing
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