White Matter transcriptome in chronic alcoholism
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE53808 | GEO | 2014/01/04
SECONDARY ACCESSION(S): PRJNA233391
REPOSITORIES: GEO
Similar Datasets
Project description:Chronic alcohol consumption can lead to alchohol-related brain damage (ARBD). Despite the well known acute effects of alcohol the mechanism responsible for chronic brain damage is largely unknown. Pathologically the major change is the loss of white matter while neuronal loss is mild and restricted to a few areas such as the prefrontal cortex. In order to improve our understanding of ARBD pathogenesis we used microarrays to explore the white matter transcriptome of alcoholics and controls. Our results suggest that hepatic encephalopathy, along with two confounders, gray matter contamination and low RNA quality, are major drivers of gene expression in ARBD. All three exceeded the effects of alcohol itself. In particular, low quality RNA samples were characterized by an upregulation of protein translation machinery while hepatic encephalopathy was associated with a downregulation of mitochondrial energy metabolism pathways. The findings in HE alcoholics are consistent with the metabolic acidosis seen in this condition. In contrast non-HE alcoholics had widespread but only subtle changes in gene expression in their white matter. The initial cohort was compromised of four alcoholics without hepatic encephalopathy (non-HE alcoholics), three alcoholics with HE (HE alcoholics) and three neurologically normal controls. For each indvidual frozen white matter was sampled in the superior frontal gyrus (prefrontal cortex) and the precentral gyrus (motor cortex). These two cortices experience either moderate (prefrontal cortex) or no neuronal loss (motor cortex) with alcohol-related brain damage. Each white matter sample was divided in two before RNA was extracted to give two 'biological' repeats and a total of 40 samples. Subsequently eight duplicates were removed due to their gray matter contamination or low RNA quality to leave a 32-sample cohort (23 alcoholic (including eight with HE ) and nine control samples.
2014-01-04 | E-GEOD-53808 | biostudies-arrayexpress
Project description:Alcohol affects gene expression in several brain regions. The amygdala is a key structure in the brainâs emotional system and in recent years the crucial importance of the amygdala in drug-seeking and relapse has been increasingly recognized. In this study gene expression screening was used to identify genes involved in alcoholism in the human basolateral amygdala. The results show that alcoholism affects a broad range of genes and many systems including genes involved in synaptic transmission, neurotransmitter transport, structural plasticity, metabolism, energy production, transcription and RNA processing and the circadian cycle. In particular, genes involved in the glutamate system were affected in the alcoholic patients. In the amygdala the glutamate system is involved in the acquisition, consolidation, expression and extinction of associative learning, which is a vital part of addiction, and in alcohol abusers it is associated with withdrawal anxiety and neurodegeneration. Downregulation of the excitatory amino acid transporters GLAST, GLT-1 and the AMPA glutamate receptor 2 (GluR2) revealed by the microarray were confirmed by Western blots. The decreased expression of GLAST, GLT-1 and GluR2 in the alcoholic patients may increase glutamate tone and activity in the basolateral amygdala and this may contribute to neurodegeneration as well as the expression of associative memories and anxiety which underlie continued drug-seeking and chronic relapse. Two-condition experiment, alcoholics vs controls. Biological replicates: 6 alcoholics 6 controls, one replicate per array.
2010-05-22 | E-GEOD-18212 | biostudies-arrayexpress
Project description:Comparison of gene expression in post-mortem hippocampus from 20 alcoholics and 19 controls. The chronic high-level alcohol consumption seen in alcoholism leads to dramatic effects on the hippocampus, including decreased white matter, loss of oligodendrocytes and other glial cells, and inhibition of neurogenesis. Examining gene expression in post mortem hippocampal tissue from 20 alcoholics and 19 controls allowed us to detect differentially expressed genes that may play a role in the risk for alcoholism or whose expression is modified by chronic consumption of alcohol. We identified 639 named genes whose expression significantly differed between alcoholics and controls at a False Discovery Rate (FDR) ≤ 0.20; 52% of these genes differed by at least 1.2-fold. Differentially expressed genes included the glucocorticoid receptor and the related gene FK506 binding protein 5 (FKBP5), UDP glycosyltransferase 8 (UGT8), urea transporter (SLC14A1), zinc transporter (SLC39A10), Interleukin 1 receptor type 1 (IL1R1), thioredoxin interacting protein (TXNIP), and many metallothioneins. Pathways related to inflammation, hypoxia, and stress showed activation, and pathways that play roles in neurogenesis and myelination showed decreases. The cortisol pathway dysregulation and increased inflammation identified here are seen in other stress-related conditions such as depression and post-traumatic stress disorder and most likely play a role in addiction. Many of the detrimental effects on the hippocampus appear to be mediated through NF-κB signaling. Twenty-four of the differentially regulated genes were previously identified by genome-wide association studies of alcohol use disorders; this raises the potential interest of genes not normally associated with alcoholism, such as suppression of tumorigenicity 18 (ST18), BCL2-associated athanogene 3 (BAG3), and von Willebrand factor (VWF).
2013-09-05 | GSE44456 | GEO
Project description:Comparison of gene expression in post-mortem hippocampus from 20 alcoholics and 19 controls. The chronic high-level alcohol consumption seen in alcoholism leads to dramatic effects on the hippocampus, including decreased white matter, loss of oligodendrocytes and other glial cells, and inhibition of neurogenesis. Examining gene expression in post mortem hippocampal tissue from 20 alcoholics and 19 controls allowed us to detect differentially expressed genes that may play a role in the risk for alcoholism or whose expression is modified by chronic consumption of alcohol. We identified 639 named genes whose expression significantly differed between alcoholics and controls at a False Discovery Rate (FDR) ? 0.20; 52% of these genes differed by at least 1.2-fold. Differentially expressed genes included the glucocorticoid receptor and the related gene FK506 binding protein 5 (FKBP5), UDP glycosyltransferase 8 (UGT8), urea transporter (SLC14A1), zinc transporter (SLC39A10), Interleukin 1 receptor type 1 (IL1R1), thioredoxin interacting protein (TXNIP), and many metallothioneins. Pathways related to inflammation, hypoxia, and stress showed activation, and pathways that play roles in neurogenesis and myelination showed decreases. The cortisol pathway dysregulation and increased inflammation identified here are seen in other stress-related conditions such as depression and post-traumatic stress disorder and most likely play a role in addiction. Many of the detrimental effects on the hippocampus appear to be mediated through NF-?B signaling. Twenty-four of the differentially regulated genes were previously identified by genome-wide association studies of alcohol use disorders; this raises the potential interest of genes not normally associated with alcoholism, such as suppression of tumorigenicity 18 (ST18), BCL2-associated athanogene 3 (BAG3), and von Willebrand factor (VWF). Comparison of gene expression from frozen human post-mortem hippocampus from 20 alcoholics and 19 controls using one array per sample. There were 6 females in each group. Sex and labeling batch were included in the analysis. The hippocampus samples came from the New South Wales Tissue Resource Centre at the University of Sydney, Australia, case ID provided for the sample. The total RNA samples were labeled in 2 balanced batches (indicated by labeling_batch). Brain sample QC provided by Tissue bank: brain pH and Post mortem interval in hours. Repoistory website: http://sydney.edu.au/medicine/pathology/trc/
2013-09-05 | E-GEOD-44456 | biostudies-arrayexpress
Project description:We compared the gene expression in post-mortem brain specimen dissected from 2 CADASIL patients with samples from 5 non-affected controls in order to discover genes differentially expressed that could be involved in the development of neuronal damage in SVD. Samples form frontal cortex and white matter and occipital cortex and white matter were used.
2015-03-12 | E-MTAB-3395 | biostudies-arrayexpress
Project description:Premature birth is frequently associated with abnormal brain development, leading to brain damage, the most common being diffuse white matter injury. Perinatal neuroinflammation, which relies primarily on microglial activation, contributes to the myelination failure by affecting oligodendrocytes. To better understand the pathophysiological mechanisms involved in encephalopathy of prematurity, we took advantage of a mouse model in which systemic injections of proinflammatory interleukin-1β (IL1B) disrupt oligodendrocyte differentiation, leading to hypomyelination and cognitive deficits. Newborn mice received intraperitoneal injections of IL1B from postnatal day (P) 1 to P5. At P5 and P10, brains were collected from six control (PBS) and six exposed (IL1B) mice; oligodendrocytes and microglial cells were sequentially isolated using antibodies coupled to magnetic beads targeting O4 and CD11b, respectively. Gene expression analysis performed on Agilent microarray revealed that perinatal inflammation induced major changes in gene expression in both cell types. By improving our understanding of the cellular mechanisms involved in encephalopathy of prematurity, this study could ultimately help design neuroprotective strategies.
2022-12-14 | GSE197563 | GEO
Project description:Hepatic Encephalopathy is the brain disorder caused by liver damage, characterized by cognitive and motor impairments. Glutamate a predominant excitatory neurotransmitter over activate post-synaptic neuron via NMDAR receptors leads to neuronal derangement. NMDAR as a therapeutic target is not viable option due to its crucial role in brain physiology. In order to discover new non-NMDAR therapeutic targets high resolution mass spectrometry (HRMS) technique was used for proteomic profiling of the hippocampal proteins in Moderate hepatic encephalopathy (MoHE) rat model.
2024-05-27 | PXD036723 | Pride
Project description:Background: The incidence of alcohol and tobacco co-abuse is as high as 80%. The molecular mechanism underlying this comorbidity is virtually unknown but interactions between these drugs have important implications for the development of, and recovery from drug dependence. Methods: We investigated the effects of chronic tobacco and alcohol abuse and the interaction of the two behaviours on global gene expression in the human nucleus accumbens using cDNA microarrays and 20 alcoholic and control cases, with and without smoking comorbidity. Changes in gene expression were established by two-way ANOVA. Unsupervised hierarchical clustering was utilized to probe the strength of the data sets. Results: Subjecting the data sets derived from microarray gene expression screening to unsupervised hierarchical clustering tied the cases into distinct groups. When considering all alcohol-responsive genes, alcoholics were separated from non alcoholics with the exception of one control case. All smokers were distinguished from non smokers based on similarity in expression of smoking-sensitive genes. In the nucleus accumbens, alcohol-responsive genes were associated with transcription, lipid metabolism and signalling. Smoking-sensitive genes were predominantly assigned to functional groups concerned with RNA processing and the endoplasmic reticulum. Both drugs influenced the expression of genes involved in matrix remodelling, proliferation and cell morphogenesis. Additionally, a gene set encoding proteins involved in the canonical pathway ‘regulation of the actin cytoskeleton’ was induced in response to alcohol and tobacco co-abuse and included. Conclusions: The region-specific modulation of alcohol-sensitive gene expression by smoking may have important consequences for alcohol-induced aberrations within the mesolimbic dopaminergic system. The data set contained individual RNA samples extracted from the nucleus accumbens from 5 non smoking non drinking control case, 5 non smoking alcoholics, 5 non drinking smokers, and 5 smoking alcoholics. An aliquot if each sample was combined to generate a reference pool. Each sample was amplified individually and labelled with Cy3 in the process, the reference samples was amplified and labelled with Cy5. Each sample was hybridised competitively against the reference sample to 1 array.
2010-07-01 | E-GEOD-20568 | biostudies-arrayexpress
Project description:Drugs of abuse including nicotine and alcohol elicit their effect by stimulating the mesocorticolimbic dopaminergic system. There is a high incidence of nicotine dependence in alcoholics. To date only limited data is available on the molecular mechanism underlying the action of alcohol and nicotine in the human brain. This study utilised gene expression screening to identify genes sensitive to chronic alcohol abuse within the ventral tegmental area of the human brain. Keywords: gene expression, brain, alcohol abuse, human, ventral tegmental area
2007-09-21 | GSE9058 | GEO
Project description:Blood-based neurofilament light (sNfL) indicates neuroaxonal injury in multiple sclerosis and is on the cusp of being implemented into clinical routine. However, anatomical origins and pathophysiological mechanisms of NfL release during acute relapses and later chronic disease stages are still poorly understood. Here, we applied immunohistochemistry, single molecule array, spatial transcriptomics and microglia/axon co-cultures to gain insight into spatio-temporal NfL release in experimental autoimmune encephalomyelitis (EAE). Results: Association of spinal cord white matter lesions and sNfL levels revealed a distinct, stage-dependent anatomical pattern of neuroaxonal damage: In chronic EAE, sNfL levels were predominately associated with anterolateral lumbar lesions, whereas in early EAE sNfL showed no correlation with lesions in any anatomical location. Furthermore, neuroaxonal damage in late EAE was largely confined to white matter lesions, but showed a widespread distribution in early EAE. Followingthis spatio-temporal pattern of neuroaxonal damage, spatial transcriptomics revealed a widespread cyto- and chemokine response at early disease stages, whereas late EAE was characterized by a prominent glial cell accumulation in white matter lesions. These findings were corroborated by immunohistochemistry and micro-glia/axon co-cultures, which further revealed a strong association between CNS myeloid cell activation and neuroaxonal damage both in vivo and in vitro. Interpretation: Our data demonstrate that sNfL release in EAE driven by CNS myeloid cells exhibits progress in a disease stage-dependent centripetal manner from normal-appearing white matter to focal white matter lesions. These findings may further aid the interpretation of elevated sNfL levels in multiple sclerosis patients at different disease stages.
2023-11-22 | GSE226591 | GEO