Developmental high binge ethanol exposure does not alter the transcriptome of visual cortical microglia as determined by mature mRNA RNA sequencing
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE97464 | GEO | 2017/09/27
SECONDARY ACCESSION(S): PRJNA381919
REPOSITORIES: GEO
Similar Datasets
Project description:Binge drinking is rising among aged adults (>65 years of age). The distinct effects of binge ethanol exposure on neurodegeneration in the aged brain are not well described. Using our model of intermittent binge ethanol exposure in young and aged mice, we investigated how binge ethanol expoure may promote neurodegenerative diease development. Spatial transcriptomics revealed that binge ethanol exposure enriched neurodegenerative disease pathways in the aged hippocampus, including tau hyperphosphorylation and neuronal death. These data suggest binge drinking during advanced aging may promote neurodegenerative disease development.
2024-03-18 | GSE236787 | GEO
Project description:We report the RNA-Seq data of microglia from CK-p25 mice visual cortex
2019-03-29 | GSE115244 | GEO
Project description:Purpose: Identify the specific transcriptome alterations in astrocytes and microglia isolated from mouse prefrontal cortex (PFC) following a chronic intermittent ethanol vapor exposure paradigm Methods: We performed RNA-sequencing on astrocytes, microglia, and total homogenate tissue isolated from the PFC of C57BL/6J mice following chronic intermittent ethanol vapor exposure Results: We identified common neuroimmune gene expression response between cell types in response to CIE, unique networks of correlated genes differentially expressed in specific cell types, along with candidate pathways, biological processes and highly connected cell-type specific genes Conclusions: This study sheds light on the cell-specific effects of chronic ethanol and provides novel molecular targets for understanding ethanol dependence
2019-08-20 | GSE128561 | GEO
Project description:Purpose: Alcohol dependence results in microglia proliferation in brain and changes in microglia morphology and function. However, it remains unknown if microglia initiate or simply amplify the neuroadaptations that lead to alcohol dependence. Here we determined microglia function in chronic intermittent ethanol exposure behaviors using a colony stimulating factor 1 receptor inhibitor (PLX5622) and 3’UTR biased-sequencing. Therefore, the purpose of this study was to provide insight into how microglia may regulate neuroadaptations due to alcohol dependence. Methods: We performed 3’UTR biased transcriptome sequencing (3’Tag-seq) on total homogenate isolated from the prefrontal cortex (PFC) and central nucleus of the amygdala (CeA) of C57BL6/J mice following microglia depletion and chronic intermittent ethanol exposure. Results: Differential expression analysis and WGCNA network analysis revealed that microglia depletion prevents both immune and synaptic gene expression changes that are linked with the formation of alcohol dependence. This suggested that microglia are key regulators of the transition from alcohol misuse to alcohol dependence. Conclusion: Taken together our behavioral and transcriptional data indicate that microglia are the primary effector cell responsible for regulation of alcohol dependence. In addition, our data represents a novel resource for groups interested in transcriptional effects of microglia depletion after alcohol dependence.
2020-11-27 | GSE142571 | GEO
Project description:Adolescence is marked in part by the ongoing development of the prefrontal cortex (PFC). Binge ethanol use during this critical stage in neurodevelopment induces significant structural changes to the PFC, as well as cognitive and behavioral deficits that can last into adulthood. Previous studies showed that adolescent binge ethanol causes lasting deficits in working memory, decreases in the expression of chromatin remodeling genes responsible for the methylation of histone 3 lysine 36 (H3K36), and global decreases in H3K36 in the PFC. H3K36me3 is present within the coding region of actively-transcribed genes, and safeguards against aberrant, cryptic transcription by RNA Polymerase II. We hypothesize that altered methylation of H3K36 could play a role in adolescent binge ethanol-induced memory deficits. To investigate this at the molecular level, ethanol (4g/kg, i.g.) or water was administered intermittently to adolescent mice. RNA- and ChIP-sequencing were then performed within the same tissue to determine gene expression changes and identify genes and loci where H3K36me3 was disrupted by ethanol. We further assessed ethanol-induced changes at the transcription level with differential exon-use and cryptic transcription analysis – a hallmark of decreased H3K36me3. Here, we found ethanol-induced changes to the gene expression and H3K36me3-regulation of synaptic-related genes in all our analyses. Notably, H3K36me3 was differentially trimethylated between ethanol and control conditions at synaptic-related genes, and Snap25 and Cplx1 showed evidence of cryptic transcription in males and females treated with ethanol during adolescence. Our results provide preliminary evidence that ethanol-induced changes to H3K36me3 during adolescent neurodevelopment may be linked to synaptic dysregulation at the transcriptional level, which may explain the reported ethanol-induced changes to PFC synaptic function.
2023-02-21 | GSE220745 | GEO
Project description:Adolescence is marked in part by the ongoing development of the prefrontal cortex (PFC). Binge ethanol use during this critical stage in neurodevelopment induces significant structural changes to the PFC, as well as cognitive and behavioral deficits that can last into adulthood. Previous studies showed that adolescent binge ethanol causes lasting deficits in working memory, decreases in the expression of chromatin remodeling genes responsible for the methylation of histone 3 lysine 36 (H3K36), and global decreases in H3K36 in the PFC. H3K36me3 is present within the coding region of actively-transcribed genes, and safeguards against aberrant, cryptic transcription by RNA Polymerase II. We hypothesize that altered methylation of H3K36 could play a role in adolescent binge ethanol-induced memory deficits. To investigate this at the molecular level, ethanol (4g/kg, i.g.) or water was administered intermittently to adolescent mice. RNA- and ChIP-sequencing were then performed within the same tissue to determine gene expression changes and identify genes and loci where H3K36me3 was disrupted by ethanol. We further assessed ethanol-induced changes at the transcription level with differential exon-use and cryptic transcription analysis – a hallmark of decreased H3K36me3. Here, we found ethanol-induced changes to the gene expression and H3K36me3-regulation of synaptic-related genes in all our analyses. Notably, H3K36me3 was differentially trimethylated between ethanol and control conditions at synaptic-related genes, and Snap25 and Cplx1 showed evidence of cryptic transcription in males and females treated with ethanol during adolescence. Our results provide preliminary evidence that ethanol-induced changes to H3K36me3 during adolescent neurodevelopment may be linked to synaptic dysregulation at the transcriptional level, which may explain the reported ethanol-induced changes to PFC synaptic function.
2023-02-21 | GSE220742 | GEO
Project description:Microglia, the resident immune cells of the brain, can exhibit a broad range of activation phenotypes, many of which have been implicated in several diseases and disorders of the central nervous system including alcohol use disorders and disorders. By utilizing a method optimized for sensitive and rapid quantitative proteomic analysis of microglia involving suspension trapping (S-Trap), we were able to produce efficient and reproducible protein extraction from low cell yielding primary mouse brains. Using a ~2 h gradient on a 75 cm UPLC column with a modified data dependent acquisition method on a hybrid quadrupole-Orbitrap mass spectrometer (QE Plus), 5,062 total proteins were identified where 4,928 of those proteins were quantifiable by label-free quantitation (with 5 biological replicates). This analysis resulted in the most comprehensive proteomic dataset for ethanol- and LPS-treated primary mouse microglia to date and even expanded upon the well-characterized macrophage/microglia response to LPS treatment. This study also highlights the subtle, yet significant changes ethanol exposure can induce when compared to control. Interestingly, these changes are not consistent with the robust classical activation induced by LPS treatment, but instead align with the emerging theory that ethanol-treated microglia yield an alternative activation response. The contrast to LPS-treated microglia leads us to conclude that ethanol does not elicit a strong inflammatory response but rather might have a general inhibitory effect on multiple pathways such as phagocytosis and cell migration.
2020-04-07 | PXD014466 | Pride
Project description:Polygenic risk scores (PRS) assess genetic susceptibility to Alcohol Use Disorder (AUD), yet their molecular implications remain underexplored. Neuroimmune interactions, particularly in microglia, are recognized as significant contributors to AUD pathophysiology. We investigated the interplay between AUD PRS and ethanol in human microglia derived from iPSCs from individuals with high-or low-PRS (HPRS or LPRS) of AUD. Ethanol exposure induced elevated CD68 expression and morphological changes in microglia, with differential responses between HPRS and LPRS microglial cells. Transcriptomic analysis revealed expression differences in MHCII complex and phagocytosis-related genes following ethanol exposure; HPRS microglial cells displayed enhanced phagocytosis and increased CLEC7Aexpression, unlike LPRS microglial cells. Synapse numbers in co-cultures of induced neurons with microglia after alcohol exposure were lower in HRPS co-cultures, suggesting possible excess synapse pruning. This study provides insights into the intricate relationship between AUD PRS, ethanol, and microglial function, potentially influencing neuronal functions in developing AUD.
2024-10-03 | GSE271585 | GEO
Project description:Polygenic risk scores (PRS) assess genetic susceptibility to Alcohol Use Disorder (AUD), yet their molecular implications remain underexplored. Neuroimmune interactions, particularly in microglia, are recognized as significant contributors to AUD pathophysiology. We investigated the interplay between AUD PRS and ethanol in human microglia derived from iPSCs from individuals with high-or low-PRS (HPRS or LPRS) of AUD. Ethanol exposure induced elevated CD68 expression and morphological changes in microglia, with differential responses between HPRS and LPRS microglial cells. Transcriptomic analysis revealed expression differences in MHCII complex and phagocytosis-related genes following ethanol exposure; HPRS microglial cells displayed enhanced phagocytosis and increased CLEC7Aexpression, unlike LPRS microglial cells. Synapse numbers in co-cultures of induced neurons with microglia after alcohol exposure were lower in HRPS co-cultures, suggesting possible excess synapse pruning. This study provides insights into the intricate relationship between AUD PRS, ethanol, and microglial function, potentially influencing neuronal functions in developing AUD.
2024-02-19 | GSE255988 | GEO
Project description:Purpose: Alcohol abuse induces changes in microglia morphology and immune function, but whether microglia initiate or simply amplify the harmful effects of alcohol exposure is still a matter of debate. Here we determined microglia function in acute and voluntary drinking behaviors using a colony stimulating factor 1 receptor inhibitor (PLX5622) and 3’UTR biased-sequencing. Therefore, The purpose of this study was to provide insight regarding microglia depletion and voluntary alcohol consumption. Methods: We performed 3’UTR biased transcriptome sequencing (3’Tag-seq) on total homogenate isolated from the prefrontal cortex (PFC) of C57BL6/J mice following microglia depletion and chronic every-other-day alcohol consumption. Results: Differential expression analysis and WGCNA network analysis revealed that although many immune genes have been implicated in alcohol abuse, downregulation of microglia genes does not necessitate changes in alcohol intake. Finally, we show that microglia depletion and chronic alcohol result in compensatory upregulation of ethanol-responsive, reactive astrocyte genes, indicating astrocytes may play a critical role in regulation of these alcohol behaviors. Conclusion:Taken together our behavioral and transcriptional data indicate that microglia are not the primary effector cell responsible for regulation of acute and voluntary alcohol behaviors. In addition, our data represents a novel resource for groups interested in transcriptional effects of microglia depletion after alcohol consumption.
2020-06-01 | GSE132516 | GEO