Alcohol Use Disorder, Neurodegeneration, Alzheimer’s and Parkinson’s Disease: Interplay Between Oxidative Stress, Neuroimmune Response and Excitotoxicity

Kamal, Haziq; Tan, Geok Chin; Ibrahim, Siti Fatimah; Shaikh, Mohd Farooq; Mohamed, Isa Naina; Mohamed, Rashidi Mohamed Pakri; Hamid, Adila A.; Ugusman, Azizah; Kumar, Jaya

doi:10.3389/fncel.2020.00282

Cited by 103 publications

(96 citation statements)

References 184 publications

(242 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…20 . Given that alcohol increases blood-brain permeability 54 and activates pro-inflammatory cytokines in the brain 55 , the association between alcohol intake and higher ISOVF (extracellular water diffusion) may be due to inflammatory demyelination. For example, higher ISOVF is evident in WM lesions of multiple sclerosis, characterized histopathologically by inflammatory demyelination associated with blood-brain permeability and axonal injury 56,57 .…”

Section: Ukb Alcoholmentioning

confidence: 99%

Multimodal brain imaging study of 36,678 participants reveals adverse effects of moderate drinking

Daviet

Aydogan

Jagannathan

et al. 2020

Preprint

View full text Add to dashboard Cite

Alcohol consumption can have significant deleterious consequences, including brain atrophy, neuronal loss, poorer white matter fiber integrity, and cognitive decline, but the effects of lightto-moderate alcohol consumption on brain structure remain unclear. Here we examine the associations between alcohol intake and brain structure using structural, diffusion tensor, and neurite orientation dispersion and density imaging data from 19,825 generally healthy middle-aged and older adults from the UK Biobank. Systematically controlling for potential confounds, we found that greater alcohol consumption was associated with lower global gray and white matter volume, regional gray matter volume in cortical and subcortical areas, and white matter fiber integrity and complexity. Post hoc analyses revealed that these associations were non-linear. Our findings extensively characterize the associations between alcohol intake and gray and white matter macrostructure and microstructure. Consuming two or more units of alcohol per day, equivalent to one drink in some establishments, could have negative effects on brain health, an important public health finding.Converging lines of research provide compelling evidence that chronic, excessive alcohol consumption is associated with global brain atrophy and regional brain changes. [1][2][3] Recent meta-analyses of magnetic resonance imaging (MRI) findings show that individuals with alcohol use disorder (AUD) have less global white matter volume (WMV) 4 and less gray matter volume (GMV) -both globally and locally in corticostriatal-limbic regions 5 -than healthy controls.Further, in a meta-analysis of pooled, multinational datasets from 33 imaging sites, individuals with AUD had lower local thickness and surface area of the hippocampus, thalamus, putamen, and amygdala than controls. 6In studies using diffusion-weighted MRI (dMRI), which allows a non-invasive investigation of white matter microstructure via measures of water molecule diffusion, individuals with AUD had lower fractional anisotropy (FA; the directional coherence of water molecule diffusion) and greater mean diffusivity (MD; the magnitude of water molecule diffusion) in the corpus callosum, frontal forceps, internal and external capsules, fornix, superior cingulate, and longitudinal fasciculi than controls. 1,7 However, because conventional dMRI measures (FA and MD) are based on a simplistic model of brain tissue microstructure, they fail to account for the complexities of neurite geometry. 8 For example, the lower FA observed in individuals with AUD 1,7 may reflect lower neurite density and/or greater orientation dispersion of neurites, which conventional dMRI measures do not differentiate. 9,10 A key question raised by prior findings in individuals with AUD that remains is whether, similar to heavy drinking, light-to-moderate alcohol consumption adversely affects brain structure. Further, is the relationship between alcohol intake and brain structure linear? In some studies of middle-aged and older adults, moderate alcoh...

show abstract

Section: Ukb Alcoholmentioning

confidence: 99%

Multimodal brain imaging study of 36,678 participants reveals adverse effects of moderate drinking

Daviet

Aydogan

Jagannathan

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Basal forebrain cholinergic neurons (BFCNs) are critically involved in cognitive function and modulation of cortical networks (Ballinger et al, 2016;Blake and Boccia, 2017;Peeters et al, 2020) due to their extensive projections to the hippocampus and multiple cortical regions (Mesulam et al, 1983;Baxter and Chiba, 1999). Adolescent binge drinking is associated with lasting consequences that persist into adulthood, including increased risk for alcohol use disorder (AUD) (Grant and Dawson, 1997) and neurodegenerative diseases, such as Alzheimer's disease (AD) (Viner and Taylor, 2007;Kamal et al, 2020). Indeed, degeneration of BFCNs and ChAT + somal shrinkage are features of several neurodegenerative disorders, including AD and AUD (Lehericy et al, 1993;Vetreno et al, 2014), and may contribute to the cognitive deficits associated with these disorders (Vogels et al, 1990;De Rosa et al, 2004;Mufson et al, 2008), all of which are also associated with increased expression of neuroimmune genes.…”

Section: Introductionmentioning

confidence: 99%

Loss of Basal Forebrain Cholinergic Neurons Following Adolescent Binge Ethanol Exposure: Recovery With the Cholinesterase Inhibitor Galantamine

Crews

Fisher

Deason

et al. 2021

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Binge drinking and alcohol abuse are common during adolescence and cause both cognitive deficits and lasting cholinergic pathology in the adult basal forebrain. Acetylcholine is anti-inflammatory and studies using the preclinical adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2 day on/2 day off from postnatal day [P]25 to P54) model of human adolescent binge drinking report decreased basal forebrain cholinergic neurons (BFCNs) and induction of proinflammatory genes that persist long into adulthood. Recent studies link AIE-induced neuroimmune activation to cholinergic pathology, but the underlying mechanisms contributing to the persistent loss of BFCNs are unknown. We report that treatment with the cholinesterase inhibitor galantamine (4.0 mg/kg, i.p.) administered during AIE (i.e., P25–P54) or following the conclusion of AIE (i.e., P57–P72) recovered the persistent loss of cholinergic neuron phenotype markers (i.e., ChAT, TrkA, and p75NTR) and somal shrinkage of residual ChAT + neurons known to persist in AIE-exposed adults. Galantamine treatment also recovered the AIE-increased expression of the proinflammatory receptors TLR4 and RAGE, the endogenous TLR4/RAGE agonist HMGB1, and the transcription activation marker pNF-κB p65. Interestingly, we find BFCNs express TLR4 and RAGE, and that AIE treatment increased pNF-κB p65 expression in adult ChAT + IR neurons, consistent with intracellular HMGB1-TLR4/RAGE signaling within BFCNs. AIE increased epigenetic transcription silencing markers (i.e., H3K9me2 and H3K9me3) in the adult basal forebrain and H3K9me2 occupancy at cholinergic phenotype gene promoters (i.e., ChAT and TrkA). The finding of no AIE-induced changes in total basal forebrain NeuN + neurons with galantamine reversal of AIE-induced ChAT + neuron loss, TLR4/RAGE-pNF-κB p65 signals, and epigenetic transcription silencing markers suggests that AIE does not cause cell death, but rather the loss of the cholinergic phenotype. Together, these data suggest that AIE induces HMGB1-TLR4/RAGE-pNF-κB p65 signals, causing the loss of cholinergic phenotype (i.e., ChAT, TrkA, and p75NTR) through epigenetic histone transcription silencing that result in the loss of the BFCN phenotype that can be prevented and restored by galantamine.

show abstract

“…Alcohol abuse has been linked to the development of mood disorders, neurodegenerative diseases, and digestive issues (Bettiol et al, 2015; Fratiglioni et al, 1993; Kamal et al, 2020; Kathryn Mchugh & Weiss, 2019; Shield et al, 2013). Given the high prevalence of alcohol abuse worldwide (World Health Organization, 2018), there is a need for effective treatments to curb the severity of its consequences.…”

Section: Introductionmentioning

confidence: 99%

Voluntary binge‐patterned alcohol drinking and sex‐specific influences on monoamine‐related neurochemical signatures in the mouse gut and brain

Shoeman

Buhr

Daniels

et al. 2021

Alcoholism Clin & Exp Res

View full text Add to dashboard Cite

Background Altered monoamine (i.e., serotonin, dopamine, and norepinephrine) activity following episodes of alcohol abuse plays key roles not only in the motivation to ingest ethanol, but also physiological dysfunction related to its misuse. Although monoamine activity is essential for physiological processes that require coordinated communication across the gut–brain axis (GBA), relatively little is known about how alcohol misuse may affect monoamine levels across the GBA. Therefore, we evaluated monoamine activity across the mouse gut and brain following episodes of binge‐patterned ethanol drinking. Methods Monoamine and select metabolite neurochemical concentrations were analyzed by ultra‐high‐performance liquid chromatography in gut and brain regions of female and male C57BL/6J mice following “Drinking in the Dark” (DID), a binge‐patterned ethanol ingestion paradigm. Results First, we found that alcohol access had an overall small effect on gut monoamine‐related neurochemical concentrations, primarily influencing dopamine activity. Second, neurochemical patterns between the small intestine and the striatum were correlated, adding to recent evidence of modulatory activity between these areas. Third, although alcohol access robustly influenced activity in brain areas in the mesolimbic dopamine system, binge exposure also influenced monoaminergic activity in the hypothalamic region. Finally, sex differences were observed in the concentrations of neurochemicals within the gut, which was particularly pronounced in the small intestine. Conclusion Together, these data provide insights into the influence of alcohol abuse and biological sex on monoamine‐related neurochemical changes across the GBA, which could have important implications for GBA function and dysfunction.

show abstract

Alcohol Use Disorder, Neurodegeneration, Alzheimer’s and Parkinson’s Disease: Interplay Between Oxidative Stress, Neuroimmune Response and Excitotoxicity

Cited by 103 publications

References 184 publications

Multimodal brain imaging study of 36,678 participants reveals adverse effects of moderate drinking

Multimodal brain imaging study of 36,678 participants reveals adverse effects of moderate drinking

Loss of Basal Forebrain Cholinergic Neurons Following Adolescent Binge Ethanol Exposure: Recovery With the Cholinesterase Inhibitor Galantamine

Voluntary binge‐patterned alcohol drinking and sex‐specific influences on monoamine‐related neurochemical signatures in the mouse gut and brain

Contact Info

Product

Resources

About