Ethanol (EtOH)‐Related Behaviors in α‐Synuclein Mutant Mice and Association of <i>SNCA</i> SNPs with Anxiety in EtOH‐Dependent Patients

Persyn, W.; Houchi, Hakim; Papillon, Charles-Antoine; Martinetti, Margaret P.; Antol, Johann; Guillaumont, Cyrille; Dervaux, Alain; Naassila, Mickaël

doi:10.1111/acer.13875

Cited by 3 publications

(3 citation statements)

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“…Alcohol use disorder (AUD), as a serious social and medical problem, could cause multiple damages to central nervous system (CNS) 1 . The effects of ethanol on CNS are associated not only with impaired learning and memory 2,3 but also with mental disorders, especially anxiety disorder and major depression disorder 4,5 . Animal experiments have also demonstrated that ethanol is an important risk factor for mental disorders such as anxiety‐like and depressive‐like behaviour 6,7 .…”

Section: Introductionmentioning

confidence: 99%

“…1 The effects of ethanol on CNS are associated not only with impaired learning and memory 2,3 but also with mental disorders, especially anxiety disorder and major depression disorder. 4,5 Animal experiments have also demonstrated that ethanol is an important risk factor for mental disorders such as anxiety-like and depressive-like behaviour. 6,7 In addition to the impairment on the brain, ethanol exposure also significantly alters the composition and function of the gut microbiota.…”

Section: Introductionmentioning

confidence: 99%

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Chronic ethanol exposure induced anxiety‐like behaviour by altering gut microbiota and GABA system

Yao

Zhang

et al. 2022

Addiction Biology

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Ethanol, also known as alcohol, is one of the most common drinks in the world. Chronic ethanol exposure has been reported to induce mental disorders. Ethanol also has a strong effect on the gut microbiota. The gut microbiota has been reported to affect the brain via multiple pathways, including changes in γ‐aminobutyric acid (GABA) system, and cause a variety of mental disorders. The GABA system in the cortex is associated with anxiety. However, the role of gut microbiota played in ethanol exposure‐induced changes in the GABA system and anxiety is still not clear. We established a 30‐day ethanol exposure mouse model and investigated the effects of microbiota using the antibiotic minocycline. Minocycline alleviated ethanol‐induced anxiety‐like behaviour, dysbiosis of microbiota, intestinal barrier disruption, increased serum endotoxin and interleukin (IL)‐6. Minocycline also attenuated ethanol‐induced apoptosis and decreased expression of glutamate decarboxylases (GADs) and GABRA1 in the prefrontal cortex. Our results indicated that gut microbiota plays an important role in ethanol‐induced anxiety‐like behaviour by altering the function of GABA system. In addition, causal mediation analysis showed that endotoxin and IL‐6 may mediate the connection between the gut microbiota and the expression of GABAA receptor in the prefrontal cortex.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chronic ethanol exposure induced anxiety‐like behaviour by altering gut microbiota and GABA system

Yao

Zhang

et al. 2022

Addiction Biology

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“…In major depressive disorder (MDD), one of the prodromal features of PD, where a 30–60% comorbidity exists with all the alpha synucleopathies, is increased α-Syn expression in blood [ 13 ]. Alpha-Syn is also linked to Alcohol Use Disorder (AUD), and some genetic variants are linked to PD, AUD as well as associated disorders such as anxiety [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Alpha-Synuclein in Alcohol Use Disorder, Connections with Parkinson’s Disease and Potential Therapeutic Role of 5’ Untranslated Region-Directed Small Molecules

et al. 2020

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Alpha-synuclein (α-Syn) is a 140-amino acid (aa) protein encoded by the Synuclein alpha SNCA gene. It is the synaptic protein associated with Parkinson’s disease (PD) and is the most highly expressed protein in the Lewy bodies associated with PD and other alpha synucleopathies, including Lewy body dementia (LBD) and multiple system atrophy (MSA). Iron deposits are present in the core of Lewy bodies, and there are reports suggesting that divalent metal ions including Cu2+ and Fe2+ enhance the aggregation of α-Syn. Differential expression of α-Syn is associated with alcohol use disorder (AUD), and specific genetic variants contribute to the risk for alcoholism, including alcohol craving. Spliced variants of α-Syn, leading to the expression of several shorter forms which are more prone to aggregation, are associated with both PD and AUD, and common transcript variants may be able to predict at-risk populations for some movement disorders or subtypes of PD, including secondary Parkinsonism. Both PD and AUD are associated with liver and brain iron dyshomeostasis. Research over the past decade has shown that α-Syn has iron import functions with an ability to oxidize the Fe3+ form of iron to Fe2+ to facilitate its entry into cells. Our prior research has identified an iron-responsive element (IRE) in the 5’ untranslated region (5’UTR) of α-Syn mRNA, and we have used the α-Syn 5’UTR to screen for small molecules that modulate its expression in the H4 neuronal cell line. These screens have led us to identify several interesting small molecules capable of both decreasing and increasing α-Syn expression and that may have the potential, together with the recently described mesenchymal stem cell therapies, to normalize α-Syn expression in different regions of the alcoholic and PD brain.

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The influence of chromosome 4 on high ethanol consumption and blood pressure

Anjos

Marchette

Kremer

et al. 2022

Alcohol

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Ethanol (EtOH)‐Related Behaviors in α‐Synuclein Mutant Mice and Association of SNCA SNPs with Anxiety in EtOH‐Dependent Patients

Abstract: Our translational study highlights a significant role of α-synuclein in components of AUD.

Cited by 3 publications

References 41 publications

Chronic ethanol exposure induced anxiety‐like behaviour by altering gut microbiota and GABA system

Chronic ethanol exposure induced anxiety‐like behaviour by altering gut microbiota and GABA system

Alpha-Synuclein in Alcohol Use Disorder, Connections with Parkinson’s Disease and Potential Therapeutic Role of 5’ Untranslated Region-Directed Small Molecules

The influence of chromosome 4 on high ethanol consumption and blood pressure

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