Alcohol reverses the effects ofKCNJ6(GIRK2) noncoding variants on excitability of human glutamatergic neurons DOI Creative Commons
Dina Popova, Isabel Gameiro‐Ros, Mark M. Youssef

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: May 24, 2022

Abstract Synonymous and noncoding single nucleotide polymorphisms (SNPs) in the KCNJ6 gene, encoding G protein-gated inwardly rectifying potassium (GIRK2) channel subunit 2, have been linked with increased electroencephalographic frontal theta event-related oscillations (ERO) subjects diagnosed alcohol use disorder (AUD). To identify molecular cellular mechanisms while retaining appropriate genetic background, we generated induced excitatory glutamatergic neurons (iN) from iPSCs derived four AUD-diagnosed variants (‘Affected: AF’) control without (‘Unaffected: UN’). Neurons were analyzed for changes gene expression, morphology, excitability physiological properties. Single cell RNA sequencing suggests that AF variant altered patterns of synaptic transmission projection morphogenesis. Results confirm express lower levels GIRK2, greater neurite area, elevated excitability. Interestingly, exposure to intoxicating concentrations ethanol induces GIRK2 expression reverses functional effects neurons. Ectopic overexpression alone mimics effect normalize We conclude decrease increase this can be minimized or reduced ethanol.

Language: Английский

“Two-step” signal amplification for ultrasensitive detection of dopamine in human serum sample using Ti3C2T -MXene DOI
Sachin Ganpat Chavan,

Pooja Ramrao Rathod,

Aneesh Koyappayil

et al.

Sensors and Actuators B Chemical, Journal Year: 2024, Volume and Issue: 404, P. 135308 - 135308

Published: Jan. 15, 2024

Language: Английский

Citations

22
Unveiling the future: Breakthroughs and innovations in MXene-based electrochemical sensors DOI
Muhammad Umer Arif Khan, Xiaohui Sun,

Faisal Attique

et al.

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: 507, P. 160392 - 160392

Published: Feb. 16, 2025

Language: Английский

Citations

2
Integrative genomics approach identifies glial transcriptomic dysregulation and risk in the cortex of individuals with Alcohol Use Disorder DOI
Anna S. Warden, Nihal A. Salem, Eric Brenner

et al.

Biological Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

1
m6A-modified lncRNA GAS5 promotes M1-polarization of microglia in alcohol use disorder DOI Creative Commons
Shuang Zhu, Peng Wang, Jian Hu

et al.

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: 221, P. 111215 - 111215

Published: Jan. 18, 2025

Long noncoding RNA (lncRNA) are essential for modulating the onset and progression of alcohol use disorder (AUD). In this study, we investigated molecular pathways through which lncRNA may contribute to AUD development. We assessed expression levels long GAS5 (lncRNA GAS5) microRNA-136-5p (miR-136-5p) in tissue samples cell lines using reverse transcription-quantitative polymerase chain reaction. Detection N6-methyladenosine (m6A) modifications, facilitated by alkylation repair homolog 5 (ALKBH5), was performed immunoprecipitation pull-down assays. The effect on functionality SH-SY5Y cells evaluated CCK-8 Transwell Our findings showed high both tissues lines. Overexpression decreased migratory capability cells, whereas silencing increased ability. Bioinformatics analyses predicted a relationship between miR-136-5p GAS5, subsequently confirmed dual-luciferase reporter Additionally, discovered that acts as sponge miR-136-5p, leading upregulation ATF2. Elevated ATF2 associated with M1 microglial polarization. summary, m6A-modified influence polarization microglia via miR-136-5p/ATF2 pathway. Statistical evaluations were GraphPad Prism V8.0, employing student's t-test comparisons two groups, assuming normal distribution equal variances. When variances unequal, but normality maintained, corrected Student's applied. non-parametric Wilcoxon rank-sum test used analyze non-normally distributed data, one-way ANOVA compare three or more groups. Independent replication ensured studies, each experiment repeated at least times statistical significance set P < 0.05.

Language: Английский

Citations

0
Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons DOI Open Access
Dina Popova, Isabel Gameiro‐Ros, Mark M. Youssef

et al.

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 28(2), P. 746 - 758

Published: Oct. 7, 2022

Language: Английский

Citations

15
Recent Advances in the Role of Non-coding RNAs in Fetal Alcohol Spectrum Disorders DOI

Ariana N. Pritha,

Andrea A. Pasmay,

Shahani Noor

et al.

Advances in experimental medicine and biology, Journal Year: 2025, Volume and Issue: unknown, P. 129 - 155

Published: Jan. 1, 2025

Language: Английский

Citations

0
Is DNA methylation in the brain a mechanism of alcohol use disorder? DOI Creative Commons
Justyna Jarczak,

Michalina Miszczak,

Kasia Radwañska

et al.

Frontiers in Behavioral Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Jan. 26, 2023

Alcohol use disorder (AUD) is a worldwide problem. Unfortunately, the molecular mechanisms of alcohol misuse are still poorly understood, therefore successful therapeutic approaches limited. Accumulating data indicate that tendency for compulsive inherited, suggesting genetic background as an important factor. However, probability to develop AUD also affected by life experience and environmental factors. Therefore, epigenetic modifications altered over lifetime likely contribute increased risk misuse. Here, we review literature looking link between DNA methylation in brain, common modification, AUD-related behaviors humans, mice rats. We sum up main findings, identify existing gaps our knowledge future directions research.

Language: Английский

Citations

6
Long Non-Coding RNAs: The New Frontier into Understanding the Etiology of Alcohol Use Disorder DOI Creative Commons

Allie N. Denham,

John W. Drake,

Matthew Gavrilov

et al.

Non-Coding RNA, Journal Year: 2022, Volume and Issue: 8(4), P. 59 - 59

Published: Aug. 4, 2022

Alcohol use disorder (AUD) is a complex, chronic, debilitating condition impacting millions worldwide. Genetic, environmental, and epigenetic factors are known to contribute the development of AUD. Long non-coding RNAs (lncRNAs) class regulatory RNAs, commonly referred as "dark matter" genome, with little no protein-coding potential. LncRNAs have been implicated in numerous processes critical for cell survival, suggesting that they play important functional roles regulating different processes. were also shown display higher tissue specificity than genes abundance brain central nervous system, demonstrating possible role etiology psychiatric disorders. Indeed, genetic (e.g., genome-wide association studies (GWAS)), molecular expression quantitative trait loci (eQTL)) from postmortem tissues identified growing list lncRNAs associated neuropsychiatric substance Given patterns widespread changes transcriptome, including methylation, chromatin architecture, activation or suppression translational activity, nature may be ubiquitous an innate component gene regulation. In this review, we present synopsis impact We discuss classifications lncRNAs, their roles, therapeutic advancements field further clarify relationship between

Language: Английский

Citations

7
Functional roles, regulatory mechanisms and theranostics applications of ncRNAs in alcohol use disorder DOI Creative Commons

Jiequan Wang,

Yaru Liu, Qingrong Xia

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(4), P. 1316 - 1335

Published: Jan. 1, 2023

Alcohol use disorder (AUD) is one of the most prevalent neuropsychological disorders worldwide, and its pathogenesis convoluted poorly understood.There considerable evidence demonstrating significant associations between multiple heritable factors onset progression AUD.In recent years, a substantial body research conducted by emerging biotechnologies has increasingly highlighted crucial roles noncoding RNAs (ncRNAs) in pathophysiology mental diseases.As in-depth understanding ncRNAs their mechanisms action, they have emerged as prospective diagnostic indicators preclinical therapeutic targets for variety psychiatric illness, including AUD.Of note, dysregulated expression such circRNAs, lncRNAs miRNAs was routinely found AUD individuals, besides, exogenous regulation partial also been shown to be effective ameliorating alcohol preference excessive consumption.However, exact molecular mechanism still remains elusive.Herein, we systematically summarized current knowledge regarding alterations certain well their-mediated regulatory individuals with AUD.And finally, detailedly reviewed potential theranostics applications gene therapy agents targeting mice.Overall, deeper comprehension functional biological may make contributions accurate diagnosis treatment AUD.

Language: Английский

Citations

4
Integrative genomics approach identifies glial transcriptomic dysregulation and risk in the cortex of individuals with Alcohol Use Disorder DOI Open Access
Anna S. Warden, Nihal A. Salem, Eric Brenner

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 17, 2024

Abstract Alcohol use disorder (AUD) is a prevalent neuropsychiatric that major global health concern, affecting millions of people worldwide. Past molecular studies AUD used underpowered single cell analysis or bulk homogenates postmortem brain tissue, which obscures gene expression changes in specific types. Here we performed nuclei RNA-sequencing 73 post-mortem samples from individuals with (N=36, N = 248,873) and neurotypical controls (N=37, 210,573) both sexes across two institutional sites. We identified 32 clusters found widespread type-specific transcriptomic the cortex AUD, particularly glia. greatest dysregulation novel microglial astrocytic subtypes accounted for majority differential co-expression modules linked to AUD. Analysis enrichment aggregate genetic risk microglia astrocytes as potential key players not only affected by but causally progression These results highlight importance cell-type offer opportunities identify targets treatment.

Language: Английский

Citations

1