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THE EFFECTS OF ALCOHOLISM ON THE HUMAN BASOLATERAL AMYGDALA

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Rosemarie Kryger

PROVIDER: E-GEOD-18212 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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THE EFFECTS OF ALCOHOLISM ON THE HUMAN BASOLATERAL AMYGDALA

Project description:Alcohol affects gene expression in several brain regions. The amygdala is a key structure in the brain’s 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.

2009-09-24 | GSE18212 | GEO

Homo sapiens

Project description:THE EFFECTS OF ALCOHOLISM ON THE HUMAN BASOLATERAL AMYGDALA

| PRJNA119581 | ENA

Gene expression profiling of high (HAB) vs. low (LAB) and normal (NAB) anxiety-related behavior mice in five laser microdissected brain regions.

Project description:Investigating the molecular basis and correlates of anxiety-related and depression-like behaviors, we generated a mouse model consisting of high (HAB), normal (NAB) and low (LAB) anxiety-related behavior mice. We utilized the elevated plus-maze for testing the genetic predisposition to anxiety-related behavior and, consequently, used this as selection criterion for the inbreeding of our animals. In depression-related tests, HAB mice display a more passive, depression-like coping strategy than LAB mice, resembling clinical comorbidity of anxiety and depression as observed in psychiatric patients. Using a microarray approach, the hypothalamic paraventricular nucleus (PVN), the basolateral (BLA) and central amygdala (CeA), the cingulate cortex (Cg) and the dentate gyrus (DG) – centers of the central nervous anxiety and fear circuitries – were investigated and screened for differences between HAB, NAB and LAB mice. Analysis was performed from four to six animals per line (HAB, NAB and LAB from generation 25, respectively) per brain region, giving a total of 78 individual arrays analyzed. The LAB mouse line is referred to as reference.

2011-05-04 | E-GEOD-29014 | biostudies-arrayexpress

Gene expression profiling of high (HAB) vs. low (LAB) anxiety-related behavior mice in seven brain regions.

Project description:Investigating the molecular basis and correlates of anxiety-related and depression-like behaviors, we generated a mouse model consisting of high (HAB) and low (LAB) anxiety-related behavior mice. We utilized the elevated plus-maze for testing the genetic predisposition to anxiety-related behavior and, consequently, used this as selection criterion for the inbreeding of our animals. In depression-related tests, HAB mice display a more passive, depression-like coping strategy than LAB mice, resembling clinical comorbidity of anxiety and depression as observed in psychiatric patients. Using a microarray approach, the hypothalamic paraventricular nucleus (PVN), the basolateral/lateral (BLA), the medial (MeA) and central amygdala (CeA), the nucleus accumbens (NAc), the cingulate cortex (Cg) and the supraoptic nucleus (SON) – centers of the central nervous anxiety and fear circuitries – were investigated and screened for differences between HAB and LAB mice. Analysis was performed from six animals per line (HAB and LAB, respectively) pooled per brain region in ten technical replicates, thereof five with a dye-swapped design giving a total of 70 array slides analyzed. The LAB mouse line is referred to as reference.

2011-08-29 | E-GEOD-28999 | biostudies-arrayexpress

Gene expression profiling of high (HAB) vs. low (LAB) and normal (NAB) anxiety-related behavior mice in five laser microdissected brain regions.

2011-05-04 | GSE29014 | GEO

Small RNA Sequencing of mouse amygdala after knockdown of miR-15a

Project description:MicroRNAs are important regulators of gene expression and associated with stress-related psychiatric disorders. We report that exposing mice to chronic stress led to a specific increase in microRNA-15a levels in the amygdala-Ago2 complex, and a concomitant reduction in the levels of its predicted target, FKBP51, which is implicated in stress-related psychiatric disorders. Reciprocally, mice expressing reduced levels of amygdalar microRNA-15a following exposure to chronic stress exhibited increased anxiety-like behaviors. Here, we performed small RNA Sequencing of mouse basolateral amygdala after miR15a knockdown using injection of a miR-15a sponge virus or control sponge virus.

2016-10-01 | GSE87533 | GEO

Gene expression profiling of high (HAB) vs. low (LAB) anxiety-related behavior mice in seven brain regions.

Project description:Investigating the molecular basis and correlates of anxiety-related and depression-like behaviors, we generated a mouse model consisting of high (HAB) and low (LAB) anxiety-related behavior mice. We utilized the elevated plus-maze for testing the genetic predisposition to anxiety-related behavior and, consequently, used this as selection criterion for the inbreeding of our animals. In depression-related tests, HAB mice display a more passive, depression-like coping strategy than LAB mice, resembling clinical comorbidity of anxiety and depression as observed in psychiatric patients. Using a microarray approach, the hypothalamic paraventricular nucleus (PVN), the basolateral/lateral (BLA), the medial (MeA) and central amygdala (CeA), the nucleus accumbens (NAc), the cingulate cortex (Cg) and the supraoptic nucleus (SON) – centers of the central nervous anxiety and fear circuitries – were investigated and screened for differences between HAB and LAB mice.

2011-08-30 | GSE28999 | GEO

Distinct contributions of ventral CA1/amygdala co-activation to the induction and maintenance of synaptic plasticity

Project description:The amygdala is known to modulate hippocampal synaptic plasticity. One role could be an immediate effect of basolateral amygdala (BLA) in priming synaptic plasticity in the hippocampus. Another role could be through associative synaptic co-operation and competition that triggers events involved in the maintenance of synaptic potentiation. We present evidence that the timing and activity level of BLA stimulation are important factors for the induction and maintenance of long-term potentiation (LTP) in ventral hippocampal area CA1. A 100 Hz BLA co-stimulation facilitated the induction of LTP, whereas 200 Hz co-stimulation attenuated induction. A 100 Hz BLA co-stimulation also caused enhanced persistence, sufficient to prevent synaptic competition. This maintenance effect is likely through translational mechanisms, as mRNA expression of primary response genes was unaffected, whereas protein level of plasticity-related products was increased. Further understanding of the neural mechanisms of amygdala modulation on hippocampus could provide insights into the mechanisms of emotional disorders.

2022-03-03 | GSE197708 | GEO

Ethanol treatment of lymphoblastoid cell lines from alcoholics and non-alcoholics causes many subtle changes in gene expression.

Project description:Compared gene expression in lymphoblasoid cell lines from alcholics and controls and 24 hr treatment with ethanol. To elucidate the effects of a controlled exposure to ethanol on gene expression, we studied lymphoblastoid cell lines (LCLs) from 21 alcoholics and 21 controls. We cultured each cell line for 24 h with and without 75 mM ethanol and measured gene expression using microarrays. Differences in expression between LCL from alcoholics and controls were modest, but included 13 genes previously identified as associated with alcoholism or related traits in one or more GWAS, including KCNA3, DICER1, ZNF415, Catalase and PPARGC1B. The paired design allowed us to detect very small changes due to ethanol treatment: ethanol altered the expression of 37% of the probe sets (51% of the unique named genes) detectably expressed in these LCLs, but most by very modest amounts. 99% of the named genes expressed in the LCLs were also expressed in at least 1 of 9 brain regions tested, suggesting that LCLs are a reasonable and accessible proxy for brain tissues. Key pathways affected by ethanol include cytokine, TNF and NF-kB signaling. Among the genes affected by ethanol were ANK3, EPHB1, SLC1A1, SLC9A9, NRD1, and SH3BP5, which were reported to be associated with alcoholism or related phenotypes in 2 genome wide association studies. Genes that either differed in expression between alcoholics and controls or were affected by ethanol exposure are candidates for further study. Lymphoblastoid cells from 21 alcoholics and 21 controls were treated with 75mM ethanol for 24 hours.

2014-10-22 | E-GEOD-52553 | biostudies-arrayexpress

Developmentally regulated sex differences in K48 polyubiquitination in the amygdala

Project description:This project examined if sex differences in K48 polyubiquitination in the amygdala were developmentally regulated. This used basolateral amygdala (BLA) samples collected from 4 and 9 week old male and female Sprague-Dawley rats.

2023-11-06 | PXD042021 | Pride

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