scholarly journals Network preservation reveals shared and unique biological processes associated with chronic alcohol abuse in NAc and PFC

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243857
Author(s):  
Eric Vornholt ◽  
John Drake ◽  
Mohammed Mamdani ◽  
Gowon McMichael ◽  
Zachary N. Taylor ◽  
...  
Keyword(s):  
Alcohol Abuse ◽  
Brain Region ◽  
Gene Networks ◽  
Transcript Level ◽  
Regulatory Elements ◽  
Biological Processes ◽  
Chronic Alcohol ◽  
Individual Gene ◽  
Chronic Alcohol Abuse ◽  
Cellular Morphogenesis

Chronic alcohol abuse has been linked to the disruption of executive function and allostatic conditioning of reward response dysregulation in the mesocorticolimbic pathway (MCL). Here, we analyzed genome-wide mRNA and miRNA expression from matched cases with alcohol dependence (AD) and controls (n = 35) via gene network analysis to identify unique and shared biological processes dysregulated in the prefrontal cortex (PFC) and nucleus accumbens (NAc). We further investigated potential mRNA/miRNA interactions at the network and individual gene expression levels to identify the neurobiological mechanisms underlying AD in the brain. By using genotyped and imputed SNP data, we identified expression quantitative trait loci (eQTL) uncovering potential genetic regulatory elements for gene networks associated with AD. At a Bonferroni corrected p≤0.05, we identified significant mRNA (NAc = 6; PFC = 3) and miRNA (NAc = 3; PFC = 2) AD modules. The gene-set enrichment analyses revealed modules preserved between PFC and NAc to be enriched for immune response processes, whereas genes involved in cellular morphogenesis/localization and cilia-based cell projection were enriched in NAc modules only. At a Bonferroni corrected p≤0.05, we identified significant mRNA/miRNA network module correlations (NAc = 6; PFC = 4), which at an individual transcript level implicated miR-449a/b as potential regulators for cellular morphogenesis/localization in NAc. Finally, we identified eQTLs (NAc: mRNA = 37, miRNA = 9; PFC: mRNA = 17, miRNA = 16) which potentially mediate alcohol’s effect in a brain region-specific manner. Our study highlights the neurotoxic effects of chronic alcohol abuse as well as brain region specific molecular changes that may impact the development of alcohol addiction.

scholarly journals Network Preservation Reveals Shared and Unique Biological Processes Associated with Chronic Alcohol Abuse in NAc and PFC

2020 ◽  
Author(s):  
Eric Vornholt ◽  
Mohammed Mamdani ◽  
John Drake ◽  
Gowon McMichael ◽  
Zachary N. Taylor ◽  
...  
Keyword(s):  
Immune Response ◽  
Alcohol Abuse ◽  
Brain Region ◽  
Health Concern ◽  
Biological Processes ◽  
Addictive Behaviors ◽  
Chronic Alcohol ◽  
Chronic Alcohol Abuse ◽  
Network Analyses ◽  
Cellular Morphogenesis

ABSTRACTBackgroundExcessive alcohol consumption has become a growing public health concern worldwide due to the potential development of alcohol dependence (AD). Prolonged alcohol abuse leads to dysregulation of the mesocorticolimbic pathway (MCL), effectively disrupting executive functioning and the allostatic conditioning of reward response.MethodsWe utilized weighted gene co-expressed network analysis (WGCNA) and network preservation using a case/control study design (n=35) to identify unique and shared biological processes dysregulated in AD in the prefrontal cortex (PFC) and nucleus accumbens (NAc). We used correlation and regression analyses to identify mRNA/miRNA interactions and local expression quantitative trait loci (cis-eQTL) to identify genetic regulatory mechanisms for networks significantly associated with AD.ResultsNetwork analyses revealed 6 and 3 significant mRNA modules from the NAc and PFC, respectively. Network preservation revealed immune response upregulation in both regions, whereas cellular morphogenesis/localization and cilia-based cell projection processes were upregulated only in the NAc. We observed 4 significantly correlated module eigengenes (ME) between the significant mRNA and miRNA modules in PFC, and 6 significant miRNA/mRNA ME correlations in NAc, with the mir-449a/b cluster emerging as a potential regulator for cellular morphogenesis/localization dysregulation in this brain region. Finally, we identified cis-eQTLs (37 mRNA and 9 miRNA in NAc, and 17 mRNA and 16 miRNA in PFC) which potentially mediate alcohol’s effect in a brain region-specific manner.ConclusionIn agreement with previous reports, we observed a generalized upregulation of immune response processes in subjects with AD, that highlights alcohol’s neurotoxic properties, while simultaneously demonstrating distinct molecular changes in subcortical brain regions as a result of chronic alcohol abuse. Such changes further support previous neuroimaging and physiological studies that emphasize the distinct roles PFC and NAc play in the development of addictive behaviors.

Effect of Chronic Alcohol Abuse on the CNS Morbidity of HIV Disease

1998 ◽  
Vol 22 (s5) ◽  
pp. 196S-200S ◽  
Author(s):  
George Fein ◽  
Daniel J. Fletcher ◽  
Victoria Sclafani
Keyword(s):  
Alcohol Abuse ◽  
Hiv Disease ◽  
Chronic Alcohol ◽  
Chronic Alcohol Abuse

Acute and Chronic Alcohol Abuse Modulate Immunity

2006 ◽  
Vol 30 (9) ◽  
pp. 1624-1631 ◽  
Author(s):  
Lou Ann S. Brown ◽  
Robert T. Cook ◽  
Thomas R. Jerrells ◽  
Jay K. Kolls ◽  
Laura E. Nagy ◽  
...  
Keyword(s):  
Alcohol Abuse ◽  
Chronic Alcohol ◽  
Chronic Alcohol Abuse

Magnetic Source Imaging in the Evaluation of Chronic Alcohol Abuse

Biomag 96 ◽  
2000 ◽  
pp. 1011-1013
Author(s):  
D. Hill ◽  
V. A. Waldorf ◽  
J. D. Lewine ◽  
S. L. Provencal ◽  
T. Moyers ◽  
...  
Keyword(s):  
Alcohol Abuse ◽  
Chronic Alcohol ◽  
Source Imaging ◽  
Magnetic Source Imaging ◽  
Chronic Alcohol Abuse ◽  
Magnetic Source

History of Chronic Alcohol Abuse Is Associated with Increased Nighttime Hypoxemia in Older Men

1987 ◽  
Vol 11 (4) ◽  
pp. 368-371 ◽  
Author(s):  
Michael V Vitiello ◽  
Patricia N Prinz ◽  
Janelle P Personius ◽  
Maureen A Nuccio ◽  
Richard K Ries ◽  
...  
Keyword(s):  
Alcohol Abuse ◽  
Older Men ◽  
Chronic Alcohol ◽  
Chronic Alcohol Abuse ◽  
History Of

Management of serious paracetamol poisoning

1988 ◽  
Vol 26 (25) ◽  
pp. 97-99
Keyword(s):  
Renal Failure ◽  
Single Dose ◽  
Alcohol Abuse ◽  
Liver Damage ◽  
Severe Pain ◽  
Paracetamol Overdose ◽  
Chronic Alcohol ◽  
Paracetamol Poisoning ◽  
Chronic Alcohol Abuse ◽  
Acute Overdose

Several hundreds of people die from paracetamol overdose each year, many perhaps unnecessarily.1 Serious poisoning usually follows acute overdose but can also occur in patients with severe pain taking large doses (over 10g/day) on consecutive days. A single dose of as little as 10g can cause hepatic or renal failure. The outcome is determined by the amount taken and, more importantly, by whether the patient comes to hospital in time for treatment to be effective.2 Chronic alcohol abuse,3 malnutrition, or taking enzyme-inducing drugs increases the risk of liver damage.4,5

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