Special Issue "Alcohol Induced Central Nervous System Damage"

A special issue of Brain Sciences (ISSN 2076-3425).

Deadline for manuscript submissions: closed (16 October 2017).

Special Issue Editor

Dr. Mark Prendergast
E-Mail Website
Guest Editor
Department of Psychology, Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, USA
Interests: neuroscience education; pedagogy; drug dependence; central nervous system damage; biochemistry; learning and memory
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Alcohol abuse and dependence produce a myriad of organ pathologies that alter both the quality and longevity of life for those affected. The central nervous system (CNS) is among the most sensitive of organ systems in this regard and pathology of the CNS has been proposed to be a key factor contributing to escalating alcohol abuse and dependence. Recent technological and theoretical advances have demonstrated that alcohol-induced CNS damage is multi-faceted in mechanism and may reflect perturbation of multiple cell signalling cascades, including those associated with innate immune activation; neuronal development and plasticity; autophagy; excitotoxicity; oxidative stress; and/or organelle function; among others. Only by investigating and understanding the full diversity of alcohol’s effect on CNS function and dysfunction will science contribute to the development of biomedical and/or biopharmaceutical interventions that may moderate alcohol-induced CNS damage and its associated behavioral correlates.

This Special Issue of Brain Sciences will provide the readers with an in-depth examination of recent and innovative findings that further our understanding of CNS damage associated with alcohol abuse and dependence. We invite you to submit contributions for this Special Issue, from both basic and applied scientific approaches, that will expand our knowledge base on this topic.

Dr. Mark A. Prendergast
Guest Editor

Manuscript Submission Information

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Keywords

  • neurodegeneration
  • atrophy
  • brain damage
  • neurological
  • fMRI

Published Papers (9 papers)

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Research

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Open AccessArticle
The GABAA Receptor α2 Subunit Activates a Neuronal TLR4 Signal in the Ventral Tegmental Area that Regulates Alcohol and Nicotine Abuse
Brain Sci. 2018, 8(4), 72; https://doi.org/10.3390/brainsci8040072 - 21 Apr 2018
Cited by 4
Abstract
Alcoholism initiates with episodes of excessive alcohol drinking, known as binge drinking, which is one form of excessive drinking (NIAAA Newsletter, 2004) that is related to impulsivity and anxiety (Ducci et al., 2007; Edenberg et al., 2004) and is also predictive of smoking [...] Read more.
Alcoholism initiates with episodes of excessive alcohol drinking, known as binge drinking, which is one form of excessive drinking (NIAAA Newsletter, 2004) that is related to impulsivity and anxiety (Ducci et al., 2007; Edenberg et al., 2004) and is also predictive of smoking status. The predisposition of non-alcohol exposed subjects to initiate binge drinking is controlled by neuroimmune signaling that includes an innately activated neuronal Toll-like receptor 4 (TLR4) signal. This signal also regulates cognitive impulsivity, a heritable trait that defines drug abuse initiation. However, the mechanism of signal activation, its function in dopaminergic (TH+) neurons within the reward circuitry implicated in drug-seeking behavior [viz. the ventral tegmental area (VTA)], and its contribution to nicotine co-abuse are still poorly understood. We report that the γ-aminobutyric acidA receptor (GABAAR) α2 subunit activates the TLR4 signal in neurons, culminating in the activation (phosphorylation/nuclear translocation) of cyclic AMP response element binding (CREB) but not NF-kB transcription factors and the upregulation of corticotropin-releasing factor (CRF) and tyrosine hydroxylase (TH). The signal is activated through α2/TLR4 interaction, as evidenced by co-immunoprecipitation, and it is present in the VTA from drug-untreated alcohol-preferring P rats. VTA infusion of neurotropic herpes simplex virus (HSV) vectors for α2 (pHSVsiLA2) or TLR4 (pHSVsiTLR4) but not scrambled (pHSVsiNC) siRNA inhibits signal activation and both binge alcohol drinking and nicotine sensitization, suggesting that the α2-activated TLR4 signal contributes to the regulation of both alcohol and nicotine abuse. Full article
(This article belongs to the Special Issue Alcohol Induced Central Nervous System Damage)
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Open AccessArticle
Behavioral and Brain Activity Indices of Cognitive Control Deficits in Binge Drinkers
Brain Sci. 2018, 8(1), 9; https://doi.org/10.3390/brainsci8010009 - 04 Jan 2018
Cited by 6
Abstract
Heavy episodic drinking is prevalent among young adults and is a public issue of increasing importance. Its initiation and maintenance are associated with deficits in the capacity to inhibit automatic processing in favor of non-habitual responses. This study used functional magnetic resonance imaging [...] Read more.
Heavy episodic drinking is prevalent among young adults and is a public issue of increasing importance. Its initiation and maintenance are associated with deficits in the capacity to inhibit automatic processing in favor of non-habitual responses. This study used functional magnetic resonance imaging (fMRI) to examine behavioral and brain activity indices of cognitive control during the Stroop task as a function of binge drinking. Heavy episodic drinkers (HED) reported consuming 5+/6+ drinks in two hours at least five times in the past six months and were compared to light drinkers (LED) who reported two or fewer binge episodes but were matched on demographics, intelligence and family history of alcoholism. Greater conflict-induced activity in the ventrolateral prefrontal cortex (VLPFC) and thalamus was observed in HED participants and it was positively correlated with alcohol intake and alcohol-related harmful consequences. HEDs maintained intact accuracy but at a cost of prolonged reaction times to high-conflict trials and increased ratings of task difficulty. Greater activation of the areas implicated in cognitive control is consistent with compensatory network expansion to meet higher cognitive demands. These results provide further insight into degradation of cognitive control in HEDs which may benefit development of detection and prevention strategies. Full article
(This article belongs to the Special Issue Alcohol Induced Central Nervous System Damage)
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Open AccessArticle
Preliminary Findings that a Targeted Intervention Leads to Altered Brain Function in Children with Fetal Alcohol Spectrum Disorder
Brain Sci. 2018, 8(1), 7; https://doi.org/10.3390/brainsci8010007 - 28 Dec 2017
Cited by 3
Abstract
Children with fetal alcohol spectrum disorder (FASD) exhibit behavioral dysregulation, executive dysfunction, and atypical function in associated brain regions. Previous research shows early intervention mitigates these outcomes but corresponding brain changes were not studied. Given the Alert® Program for Self-Regulation improves behavioral [...] Read more.
Children with fetal alcohol spectrum disorder (FASD) exhibit behavioral dysregulation, executive dysfunction, and atypical function in associated brain regions. Previous research shows early intervention mitigates these outcomes but corresponding brain changes were not studied. Given the Alert® Program for Self-Regulation improves behavioral regulation and executive function in children with FASD, we asked if this therapy also improves their neural functioning in associated regions. Twenty-one children with FASD aged 8–12 years were randomized to the Alert®-treatment (TXT; n = 10) or waitlist-control (WL; n = 11) conditions. They were assessed with a Go-NoGo functional magnetic resonance imaging (fMRI) paradigm before and after training or the wait-out period. Groups initially performed equivalently and showed no fMRI differences. At post-test, TXT outperformed WL on NoGo trials while fMRI in uncorrected results with a small-volume correction showed less activation in prefrontal, temporal, and cingulate regions. Groups also demonstrated different patterns of change over time reflecting reduced signal at post-test in selective prefrontal and parietal regions in TXT and increased in WL. In light of previous evidence indicating TXT at post-test perform similar to non-exposed children on the Go-NoGo fMRI paradigm, our findings suggest Alert® does improve functional integrity in the neural circuitry for behavioral regulation in children with FASD. Full article
(This article belongs to the Special Issue Alcohol Induced Central Nervous System Damage)
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Open AccessArticle
Binge Alcohol Exposure Transiently Changes the Endocannabinoid System: A Potential Target to Prevent Alcohol-Induced Neurodegeneration
Brain Sci. 2017, 7(12), 158; https://doi.org/10.3390/brainsci7120158 - 29 Nov 2017
Cited by 3
Abstract
Excessive alcohol consumption leads to neurodegeneration, which contributes to cognitive decline that is associated with alcohol use disorders (AUDs). The endocannabinoid system has been implicated in the development of AUDs, but little is known about how the neurotoxic effects of alcohol impact the [...] Read more.
Excessive alcohol consumption leads to neurodegeneration, which contributes to cognitive decline that is associated with alcohol use disorders (AUDs). The endocannabinoid system has been implicated in the development of AUDs, but little is known about how the neurotoxic effects of alcohol impact the endocannabinoid system. Therefore, the current study investigated the effects of neurotoxic, binge-like alcohol exposure on components of the endocannabinoid system and related N-acylethanolamines (NAEs), and then evaluated the efficacy of fatty acid amide hydrolase (FAAH) inhibition on attenuating alcohol-induced neurodegeneration. Male rats were administered alcohol according to a binge model, which resulted in a transient decrease in [3H]-CP-55,940 binding in the entorhinal cortex and hippocampus following two days, but not four days, of treatment. Furthermore, binge alcohol treatment did not change the tissue content of the three NAEs quantified, including the endocannabinoid and anandamide. In a separate study, the FAAH inhibitor, URB597 was administered to rats during alcohol treatment and neuroprotection was assessed by FluoroJade B (FJB) staining. The administration of URB597 during binge treatment did not significantly reduce FJB+ cells in the entorhinal cortex or hippocampus, however, a follow up “target engagement” study found that NAE augmentation by URB597 was impaired in alcohol intoxicated rats. Thus, potential alcohol induced alterations in URB597 pharmacodynamics may have contributed to the lack of neuroprotection by FAAH inhibition. Full article
(This article belongs to the Special Issue Alcohol Induced Central Nervous System Damage)
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Open AccessArticle
Adolescent Alcohol Drinking Renders Adult Drinking BLA-Dependent: BLA Hyper-Activity as Contributor to Comorbid Alcohol Use Disorder and Anxiety Disorders
Brain Sci. 2017, 7(11), 151; https://doi.org/10.3390/brainsci7110151 - 14 Nov 2017
Cited by 5
Abstract
Adolescent alcohol drinking increases the risk for alcohol-use disorder in adulthood. Yet, the changes in adult neural function resulting from adolescent alcohol drinking remain poorly understood. We hypothesized that adolescent alcohol drinking alters basolateral amygdala (BLA) function, making alcohol drinking BLA-dependent in adulthood. [...] Read more.
Adolescent alcohol drinking increases the risk for alcohol-use disorder in adulthood. Yet, the changes in adult neural function resulting from adolescent alcohol drinking remain poorly understood. We hypothesized that adolescent alcohol drinking alters basolateral amygdala (BLA) function, making alcohol drinking BLA-dependent in adulthood. Male, Long Evans rats were given voluntary, intermittent access to alcohol (20% ethanol) or a bitter, isocaloric control solution, across adolescence. Half of the rats in each group received neurotoxic BLA lesions. In adulthood, all rats were given voluntary, intermittent access to alcohol. BLA lesions reduced adult alcohol drinking in rats receiving adolescent access to alcohol, but not in rats receiving adolescent access to the control solution. The effect of the BLA lesion was most apparent in high alcohol drinking adolescent rats. The BLA is essential for fear learning and is hyper-active in anxiety disorders. The results are consistent with adolescent heavy alcohol drinking inducing BLA hyper-activity, providing a neural mechanism for comorbid alcohol use disorder and anxiety disorders. Full article
(This article belongs to the Special Issue Alcohol Induced Central Nervous System Damage)
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Open AccessArticle
Investigation of Sex Differences in the Microglial Response to Binge Ethanol and Exercise
Brain Sci. 2017, 7(10), 139; https://doi.org/10.3390/brainsci7100139 - 24 Oct 2017
Cited by 10
Abstract
The female brain appears selectively vulnerable to the neurotoxic effects of alcohol, but the reasons for this are unclear. One possibility is an exaggerated neuroimmune response in the female brain, such that alcohol increases microglia number and reactivity to subsequent stimuli, such as [...] Read more.
The female brain appears selectively vulnerable to the neurotoxic effects of alcohol, but the reasons for this are unclear. One possibility is an exaggerated neuroimmune response in the female brain, such that alcohol increases microglia number and reactivity to subsequent stimuli, such as exercise. It is important to better characterize the interactive neural effects of alcohol and exercise, as exercise is increasingly being used in the treatment of alcohol use disorders. The present study compared the number of microglia and evidence of their activation in alcohol-vulnerable regions of the brain (medial prefrontal cortex and hippocampus) in male and female rats following binge alcohol and/or exercise. Binge alcohol increased microglia number and morphological characteristics consistent with their activation in the female brain but not the male, regardless of exercise. Binge alcohol followed by exercise did increase the number of MHC II+ (immunocompetent) microglia in females, although the vast majority of microglia did not express MHC II. These results indicate that binge alcohol exerts sex-specific effects on microglia that may result in enhanced reactivity to a subsequent challenge and in part underlie the apparent selective vulnerability of the female brain to alcohol. Full article
(This article belongs to the Special Issue Alcohol Induced Central Nervous System Damage)
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Open AccessArticle
Impact of Prenatal and Subsequent Adult Alcohol Exposure on Pro-Inflammatory Cytokine Expression in Brain Regions Necessary for Simple Recognition Memory
Brain Sci. 2017, 7(10), 125; https://doi.org/10.3390/brainsci7100125 - 30 Sep 2017
Cited by 8
Abstract
Microglia, the immune cells of the brain, are important and necessary for appropriate neural development; however, activation of microglia, concomitant with increased levels of secreted immune molecules during brain development, can leave the brain susceptible to certain long-term changes in immune function associated [...] Read more.
Microglia, the immune cells of the brain, are important and necessary for appropriate neural development; however, activation of microglia, concomitant with increased levels of secreted immune molecules during brain development, can leave the brain susceptible to certain long-term changes in immune function associated with neurological and developmental disorders. One mechanism by which microglia can be activated is via alcohol exposure. We sought to investigate if low levels of prenatal alcohol exposure can alter the neuroimmune response to a subsequent acute dose of alcohol in adulthood. We also used the novel object location and recognition memory tasks to determine whether there are cognitive deficits associated with low prenatal alcohol exposure and subsequent adulthood alcohol exposure. We found that adult rats exposed to an acute binge-like level of alcohol, regardless of gestational alcohol exposure, have a robust increase in the expression of Interleukin (IL)-6 within the brain, and a significant decrease in the expression of IL-1β and CD11b. Rats exposed to alcohol during gestation, adulthood, or at both time points exhibited impaired cognitive performance in the cognitive tasks. These results indicate that both low-level prenatal alcohol exposure and even acute alcohol exposure in adulthood can significantly impact neuroimmune and associated cognitive function. Full article
(This article belongs to the Special Issue Alcohol Induced Central Nervous System Damage)
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Review

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Open AccessReview
Long Term Depression in Rat Hippocampus and the Effect of Ethanol during Fetal Life
Brain Sci. 2017, 7(12), 157; https://doi.org/10.3390/brainsci7120157 - 28 Nov 2017
Cited by 8
Abstract
Alcohol (ethanol) disturbs cognitive functions including learning and memory in humans, non-human primates, and laboratory animals such as rodents. As studied in animals, cellular mechanisms for learning and memory include bidirectional synaptic plasticity, long-term potentiation (LTP), and long-term depression (LTD), primarily in the [...] Read more.
Alcohol (ethanol) disturbs cognitive functions including learning and memory in humans, non-human primates, and laboratory animals such as rodents. As studied in animals, cellular mechanisms for learning and memory include bidirectional synaptic plasticity, long-term potentiation (LTP), and long-term depression (LTD), primarily in the hippocampus. Most of the research in the field of alcohol has analyzed the effects of ethanol on LTP; however, with recent advances in the understanding of the physiological role of LTD in learning and memory, some authors have examined the effects of ethanol exposure on this particular signal. In the present review, I will focus on hippocampal LTD recorded in rodents and the effects of fetal alcohol exposure on this signal. A synthesis of the findings indicates that prenatal ethanol exposure disturbs LTD concurrently with LTP in offspring and that both glutamatergic and γ-aminobutyric acid (GABA) neurotransmissions are altered and contribute to LTD disturbances. Although the ultimate mode of action of ethanol on these two transmitter systems is not yet clear, novel suggestions have recently appeared in the literature. Full article
(This article belongs to the Special Issue Alcohol Induced Central Nervous System Damage)
Open AccessReview
Platelet Endothelial Cell Adhesion Molecule-1 and Oligodendrogenesis: Significance in Alcohol Use Disorders
Brain Sci. 2017, 7(10), 131; https://doi.org/10.3390/brainsci7100131 - 16 Oct 2017
Cited by 4
Abstract
Alcoholism is a chronic relapsing disorder with few therapeutic strategies that address the core pathophysiology. Brain tissue loss and oxidative damage are key components of alcoholism, such that reversal of these phenomena may help break the addictive cycle in alcohol use disorder (AUD). [...] Read more.
Alcoholism is a chronic relapsing disorder with few therapeutic strategies that address the core pathophysiology. Brain tissue loss and oxidative damage are key components of alcoholism, such that reversal of these phenomena may help break the addictive cycle in alcohol use disorder (AUD). The current review focuses on platelet endothelial cell adhesion molecule 1 (PECAM-1), a key modulator of the cerebral endothelial integrity and neuroinflammation, and a targetable transmembrane protein whose interaction within AUD has not been well explored. The current review will elaborate on the function of PECAM-1 in physiology and pathology and infer its contribution in AUD neuropathology. Recent research reveals that oligodendrocytes, whose primary function is myelination of neurons in the brain, are a key component in new learning and adaptation to environmental challenges. The current review briefly introduces the role of oligodendrocytes in healthy physiology and neuropathology. Importantly, we will highlight the recent evidence of dysregulation of oligodendrocytes in the context of AUD and then discuss their potential interaction with PECAM-1 on the cerebral endothelium. Full article
(This article belongs to the Special Issue Alcohol Induced Central Nervous System Damage)
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