Zinc deficiency as a mediator of toxic effects of alcohol abuse

Skalny, Anatoly V.; Skalnaya, Margarita G.; Grabeklis, Andrei R.; Skalnaya, Anastasia A.; Tinkov, Alexey A.

doi:10.1007/s00394-017-1584-y

Cited by 50 publications

(32 citation statements)

References 106 publications

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“…In a meta-analysis of nine studies, a high dietary zinc intake appears to be linked to better protection against depression, with a meaningful relative risk of 0.67 (95% confidence interval: 0.58-0.76); associations were significant both in cross-sectional and in prospective studies [192]. Zinc deficiency is suspected to be a mediator of toxic effects of alcohol abuse, including at the brain level, and zinc status is generally low in alcoholic patients [193]. As for iron, zinc overload may be deleterious to brain functions: in patients suffering from Alzheimer disease, zinc at physiological levels suppresses β-amyloid-induced neurotoxicity by selectively precipitating aggregation intermediates; however, at high levels, the binding of zinc to β-amyloid may rather enhance fibrillar β-amyloid aggregation, leading to neurodegeneration [194].…”

Section: Intake or Status In Vitamin C Iron Magnesium And Zinc And mentioning

confidence: 96%

Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence

et al. 2020

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Vitamins and minerals are essential to humans as they play essential roles in a variety of basic metabolic pathways that support fundamental cellular functions. In particular, their involvement in energy-yielding metabolism, DNA synthesis, oxygen transport, and neuronal functions makes them critical for brain and muscular function. These, in turn, translate into effects on cognitive and psychological processes, including mental and physical fatigue. This review is focused on B vitamins (B1, B2, B3, B5, B6, B8, B9 and B12), vitamin C, iron, magnesium and zinc, which have recognized roles in these outcomes. It summarizes the biochemical bases and actions of these micronutrients at both the molecular and cellular levels and connects them with cognitive and psychological symptoms, as well as manifestations of fatigue that may occur when status or supplies of these micronutrients are not adequate.

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Section: Intake or Status In Vitamin C Iron Magnesium And Zinc And mentioning

confidence: 96%

Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence

et al. 2020

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“…Interestingly, Zn 2+ binds to NMDA and AMPA receptors (40,41) and it is likely that, in addition to DA signaling, cocaineinduced changes in synaptic Zn 2+ may exert allosteric interactions at ionotropic glutamate receptors to influence cocaine-dependent glutamate neurotransmission and behaviors such as cocaine locomotor sensitization and cocaine priming-induced reinstatement of cocaine seeking (23,24,42). Finally, we propose that the cocaine-dependent changes in Zn 2+ that we describe here are not specific to cocaine but can be elicited by other psychostimulants that modulate DAT function and increase corticostriatal glutamate neurotransmission (23,24,43), and potentially other drugs of abuse, including alcohol (44) Finally, in addition to its critical role in addiction, the DAT is the primary molecular target for stimulant medications used in the treatment of attention-deficit hyperactivity disorder (ADHD).…”

Section: Discussionmentioning

confidence: 75%

Synaptic Zn²⁺potentiates the effects of cocaine on striatal dopamine neurotransmission and behavior

Gómez

Bonaventura

Keighron

et al. 2020

Preprint

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Cocaine binds to the dopamine transporter (DAT) in the striatum to regulate cocaine reward and seeking behavior. Zinc (Zn2+) also binds to the DAT, but the in vivo relevance of this interaction is unknown. We found that cocaine abuse in humans correlated with low postmortem striatal Zn2+ content. In mice, cocaine decreased striatal vesicular Zn2+ and increased striatal synaptic Zn2+ concentrations and Zn2+ uptake. Striatal synaptic Zn2+ increased cocaine’s in vivo potency at the DAT and was required for cocaine-induced DAT upregulation. Finally, genetic or dietary Zn2+ manipulations modulated cocaine locomotor sensitization, conditioned place preference, self-administration, and reinstatement. These findings reveal new insights into cocaine’s pharmacological mechanism of action and indicate that Zn2+ can serve as a critical environmentally derived regulator of human cocaine addiction.

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“…The interaction between Zn 2+ and NMDAR activity has shown to be an important contributor to synaptic plasticity through regulating postsynaptic density assembly [34]. It is well understood that chronic alcohol abuse leads to varying degrees of organ-wide zinc deficiency [35], but the neurobiological consequences of how zinc deficiency in the brain contributes to AD etiology is poorly understood. The upregulation of brain metallothionines in response to the alcohol oxidative damage may contribute to this zinc homeostatic imbalance, altering synaptic signaling cascades and effectively the behavior.…”

Section: Discussionmentioning

confidence: 99%

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

Vornholt

Mamdani

Drake³

et al. 2020

Preprint

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Background: Excessive 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. Methods:We 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.Results: Network 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. Conclusion:In 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. MAIN TEXT Introduction:Alcohol use disorder (AUD) is a debilitating psychiatric illness with negative health, economic, and social consequences for nearly 15.1 million affected adults worldwide [1]. AUD risk is dependent upon both genetic and environmental factors, with a heritability of 0.49 [2]. The neurobiological framework for understanding how benign, recreational alcohol use leads to AUD follows various theories [3-5], with the most commonly accepted being the cyclical model of addiction [6]. This theory provides valuable insight into the functional specialization of different brain regions that underlie behavioral maladaptations associated with AUD [7]. However, the genetic architecture and molecular mechanisms contributing to alcohol-facilitated neuroadaptations remain widely unknown.Postmortem brain studies provide the unique opportunity to interrogate neurobiological changes associated with addiction across brain regions and neural pathways [8,9]...

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Zinc deficiency as a mediator of toxic effects of alcohol abuse

Abstract: Generally, current findings suggest that assessment of Zn status could be used as a diagnostic marker of metabolic disturbances in alcohol abuse, whereas modulation of Zn metabolism may be a potential tool in the treatment of alcohol-associated disorders.

Cited by 50 publications

References 106 publications

Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence

Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence

Synaptic Zn²⁺potentiates the effects of cocaine on striatal dopamine neurotransmission and behavior

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

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Zinc deficiency as a mediator of toxic effects of alcohol abuse

Abstract: Generally, current findings suggest that assessment of Zn status could be used as a diagnostic marker of metabolic disturbances in alcohol abuse, whereas modulation of Zn metabolism may be a potential tool in the treatment of alcohol-associated disorders.

Cited by 50 publications

References 106 publications

Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence

Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence

Synaptic Zn2+potentiates the effects of cocaine on striatal dopamine neurotransmission and behavior

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

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Synaptic Zn²⁺potentiates the effects of cocaine on striatal dopamine neurotransmission and behavior