Effects of chronic intermittent ethanol exposure and withdrawal on neuroblastoma cell transcriptome.
paper
Primary
Public
- Authors
- McClintick, Jeanette N; Thapa, Kriti; Liu, Yunlong; Xuei, Xiaoling; Edenberg, Howard J
- Year
- 2020
- Journal
- Alcohol (Fayetteville, N.Y.)
- PMID
- 31923563
- DOI
- 10.1016/j.alcohol.2019.12.004
- PMCID
- PMC7237278
Cycles of heavy drinking and abstinence can lead to alcohol use disorder. We studied the effects of chronic intermittent ethanol exposure (CIE) over 3 weeks on neuroblastoma cells, using an ethanol concentration frequently attained in binge drinking (40Β mM, 184Β mg/dL). There were many changes in gene expression but most were small. CIE affected pathways instrumental in the development or plasticity of neurons, including axonal guidance, reelin signaling, and synaptogenesis. Genes involved in dopamine and serotonin signaling were also affected. Changes in transporters and receptors could dampen both NMDA and norepinephrine transmissions. Decreased expression of the GABA transporter SLC6A11 could increase GABA transmission and has been associated with a switch from sweet drinking to ethanol consumption in rats. Ethanol increased stress responses such as the unfolded protein response. TGF-Ξ² and NFΞΊB signaling were increased. Most of the genes involved in cholesterol biosynthesis were decreased in expression. Withdrawal for 24Β h after CIE caused most of the CIE-induced expression changes to move back toward unexposed levels.
Scatter plot of log2 ratios comparing ethanol treatment to control (y-axis) and ethanol treatment to ethanol plus 24h withdrawal (x-axis). Genes shown differ in expression between ethanol vs. control at FDR < 0.20.
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| Name | Type |
|---|---|
| acute exposure local | phenotype |
| ADCY | gene |
| ADCY1 | gene |
| ADCY3 | gene |
| ADCY6 | gene |
| ADCY9 | gene |
| ADH5 | gene |
| adolescent P rats local | cohort |
| ADRA2A | gene |
| ADRA2C local | gene |
| alcohol | phenotype |
| Alcoholic LCLs local | cohort |
| alcoholism | phenotype |
| Alcohol Use Disorder | phenotype |
| amygdala | anatomy |
| astrocytes | phenotype |
| ATF4 | gene |
| axonal guidance | phenotype |
| basolateral amygdala | anatomy |
| binge drinking | phenotype |
| blood alcohol levels | phenotype |
| brain | anatomy |
| brain development | phenotype |
| brain tissue | anatomy |
| C5 local | gene |
| C57BL/6J | cohort |
| CACNA2D2 | gene |
| cAMP | drug |
| CCL5 | gene |
| cDNA | drug |
| cell cycle | phenotype |
| cholesterol biosynthesis | phenotype |
| cholesterol biosynthesis genes local | gene |
| cholesterol_pathway local | phenotype |
| chronic ethanol exposure | phenotype |
| chronic intermittent ethanol exposure withdrawn local | phenotype |
| chronic intermittent exposure to ethanol local | drug |
| CIE | drug |
| CIE cells local | cohort |
| CIE exposure local | drug |
| CIE treated P rats local | cohort |
| CIE-treated samples local | cohort |
| CIE treatment local | drug |
| COMT | gene |
| control | cohort |
| control group | cohort |
| Control LCLs local | cohort |
| controls | cohort |
| Cyclins local | gene |
| DBH | gene |
| DDC | gene |
| dexamethasone | drug |
| dopamine | drug |
| dopamine signaling | phenotype |
| dorsal raphe nucleus | anatomy |
| DRD2 | gene |
| d-serine | drug |
| EFNB2 local | gene |
| EMEM local | drug |
| EPHA2 local | gene |
| EPHB4 local | gene |
| Ephrin receptors local | gene |
| epithelial to mesenchymal transition local | phenotype |
| estrogen receptor | gene |
| ethanol consumption | phenotype |
| ethanol withdrawal | phenotype |
| F12K medium local | drug |
| fetal bovine serum | drug |
| FGFR1 | gene |
| FGFR2 | gene |
| FGF receptors local | gene |
| Frizzled receptors local | gene |
| frontal cortex | anatomy |
| functional connectivity | phenotype |
| FZD local | gene |
| FZD2 local | gene |
| FZD4 local | gene |
| FZD5 local | gene |
| FZD7 local | gene |
| GAB1 local | gene |
| GABA | phenotype |
| gene expression | phenotype |
| glutamate | drug |
| glutamate signaling | phenotype |
| glycine | drug |
| Grb2 | gene |
| GRIA2 | gene |
| GRM2 | gene |
| GRM7 | gene |
| GRM8 | gene |
| GTEx | cohort |
| GTEx consortium | cohort |
| HAD rat strain local | cohort |
| HIF1A local | gene |
| high blood alcohol levels local | phenotype |
| High intensity drinking local | phenotype |
| hippocampus | anatomy |
| HMGCR | gene |
| IL11 local | gene |
| increased ethanol intake local | phenotype |
| inflammatory response | phenotype |
| INSIG1 local | gene |
| insulin receptor local | gene |
| IRS1 | gene |
| LCLs of alcoholics local | cohort |
| LTB4 | drug |
| LTB4R local | gene |
| lymphoblastoid cell lines | cohort |
| MAOB | gene |
| MAP2K1 | gene |
| MAP2K12 local | gene |
| MAP3K1 local | gene |
| MAP3K3 local | gene |
| MAPK | gene |
| Mapk1 | gene |
| MAPK12 local | gene |
| MCM complex local | gene |
| mice | cohort |
| microglia | phenotype |
| neuroblastoma | phenotype |
| neuroblastoma cell line local | phenotype |
| neurogenesis | phenotype |
| neuronal differentiation | phenotype |
| neuron cell death local | phenotype |
| neuron function or development local | phenotype |
| neurons | phenotype |
| NFE2L2 local | gene |
| NFΞΊB | gene |
| NFΞΊB1 local | gene |
| norepinephrine | drug |
| norepinephrine release local | phenotype |
| nucleus accumbens | anatomy |
| Oprd1 | cohort |
| OPRL1 | cohort |
| OPRM1 | cohort |
| penicillin | drug |
| periaqueductal gray | anatomy |
| phosphate-buffered saline | drug |
| Plexins local | gene |
| pluripotency | phenotype |
| polyA RNA local | drug |
| post-synapse local | phenotype |
| P rats | cohort |
| P rat strain local | cohort |
| prefrontal cortex | anatomy |
| proinflammatory effect local | phenotype |
| RARA | gene |
| RNA | drug |
| Semaphorins local | gene |
| serotonin | drug |
| SH-SY5Y local | cohort |
| SH-SY5Y neuroblastoma cells local | cohort |
| Slc1a2 | gene |
| SLC1A4 local | gene |
| SLC6A11 | gene |
| SLC6A2 | gene |
| SLC6A9 | gene |
| SREBF1 | gene |
| SREBF2 | gene |
| streptomycin | drug |
| sweet drinking rats local | cohort |
| synapse | anatomy |
| synapse part local | phenotype |
| synaptic plasticity | phenotype |
| synaptogenesis | phenotype |
| temporal cortex | anatomy |
| Tlr4 | gene |
| TP53 | gene |
| treatment samples | cohort |
| Tubulins local | gene |
| Unexposed cells local | cohort |
| unfolded protein response local | phenotype |
| United States | cohort |
| US adults 2012-2013 | cohort |
| various brain regions local | anatomy |
| ventral hippocampus | anatomy |
| WNT | gene |
| WNT5A local | gene |
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| Integrated single-cell multiomic profiling of caudate nucleus suggests key mechanisms in alcohol use disorder. | Green NC et al. | β | 2025 | β |
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