Neuroimmune pathways as targets to reduce alcohol consumption

Grantham, Emily K.; Barchiesi, Riccardo; Salem, Nihal A.; Mayfield, R. Dayne

doi:10.1016/j.pbb.2022.173491

Cited by 2 publications

(3 citation statements)

References 23 publications

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“…(iii) Human intra-species comparison between the three brain areas suggests five potential biomarkers for AUD (e.g., SERPINA3). (iv) The most consistent finding across all meta-analyses performed here is the dysregulation of numerous genes encoding inflammatory processes and BBB integrity; in conjunction with the cell type-specific accumulation of these DEGs in astrocytes, microglia and endothelial cells, this finding is consistent with the proposed critical role of inflammatory mechanisms in AUD [46][47][48][49] .…”

Section: Discussionsupporting

confidence: 81%

“…Furthermore, the cell type-specific enrichment in glia cells, such as astrocytes underlines the overrepresentation of inflammatory mechanisms in the PFC of AUD individuals. This finding is in line with one of the key hypotheses in the field, namely that glial cells, such as astrocytes and microglia, are considered as new cellular targets for treating alcohol-induced inflammatory and behavioral responses (Crews et al, 2017;Erickson et al, 2019;Grantham et al, 2023).…”

Section: Meta-analysis Of the Human And Rodent Pfc Led To The Majorit...supporting

confidence: 84%

“…The main finding is that a majority of DEGs is enriched in inflammatory processes. Previous research has repeatedly shown that especially inflammation -related genes are up-regulated in alcohol dependence [46][47][48] . And furthermore, that neuroinflammatory processes indeed promote AUD development and progression 49,50 .…”

Section: Meta-analysis Of the Human And Rodent Pfc Led To The Majorit...mentioning

confidence: 99%

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A Systematic Review and Meta-analysis on the Transcriptomic Signatures in Alcohol Use Disorder

Friske

Torrico

Borruto

et al. 2022

Preprint

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Alcohol Use Disorder (AUD) is a complex mental disease with a large treatment need. However, the clinically available therapeutic approaches are limited and thus new treatment targets are warranted. One approach to discover new treatment targets is transcriptomic profiling of key brain regions of the addiction neurocircuitry in animal models of AUD and/or in post-mortem brain tissue from deceased AUD patients. Unfortunately, those studies suffer from large heterogeneity and low sample sizes. Here we used a cross-species meta-analysis that integrates the entire literature on this topic to make more robust conclusions on transcriptomic changes in AUD. Here, we report on differentially expressed genes (DEGs) in 108 rat brain and 380 human brain samples, respectively in one of the key regions of AUD- the prefrontal cortex. We found 50 differentially expressed genes (DEGs) in rat brain, which were mainly associated with pro-oncogenic molecules, signal transduction as well as oxidative stress and inflammation. When we compared these findings with the meta-analytic results in human post-mortem PFC, we found that across species Hsd11b1 is significantly down-regulated. This finding is also confirmed by our cross-species data integrational approach. In summary, our data suggests that down-regulation of Hsd11b1 enzyme and stress-related pathways is a conserved mechanism for the alcohol dependent phenotype across different species, which might explain increased cortisol levels in AUD and therefore serves as a new treatment target.

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Section: Discussionsupporting

confidence: 81%

Section: Meta-analysis Of the Human And Rodent Pfc Led To The Majorit...supporting

confidence: 84%