Cross-species epigenetic regulation of nucleus accumbens KCNN3 transcripts by excessive ethanol drinking. DOI Creative Commons

Rita Cervera Juanes,

Patrick J. Mulholland,

Audrey E. Padula

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Сен. 15, 2023

The underlying genetic and epigenetic mechanisms driving functional adaptations in neuronal excitability excessive alcohol intake are poorly understood. Small-conductance Ca2+-activated K+ (KCa2 or SK) channels encoded by the KCNN family of genes have emerged from preclinical studies as a key contributor to alcohol-induced neuroadaptations alcohol-drinking monkeys dependent mice. Here, this cross-species analysis focused on KCNN3 DNA methylation, gene expression, single nucleotide polymorphisms including alternative promoters that could influence surface trafficking function KCa2 channels. Bisulfite sequencing nucleus accumbens tissue mice revealed differentially methylated region exon 1A overlaps with predicted promoter sequence. hypermethylation paralleled an increase expression transcripts encode apamin-insensitive dominant-negative channel isoforms. A polymorphic repeat macaque 1 did not correlate drinking. At protein level, KCa2.3 was significantly reduced very heavy drinking monkeys. Together, our findings dysregulation represent complex mechanism utilizes impact firing neurons. Thus, these results provide support for possible molecular harmful use disorder.

Язык: Английский

Epigenetic drugs and psychedelics as emerging therapies for alcohol use disorder: insights from preclinical studies DOI
Fahd François Hilal, Jérôme Jeanblanc, Chloé Deschamps

и другие.

Journal of Neural Transmission, Год журнала: 2024, Номер 131(5), С. 525 - 561

Опубликована: Март 30, 2024

Язык: Английский

Процитировано

4
Cross-species epigenetic regulation of nucleus accumbens KCNN3 transcripts by excessive ethanol drinking DOI Creative Commons
Patrick J. Mulholland,

Audrey E. Padula,

Larry Wilhelm

и другие.

Translational Psychiatry, Год журнала: 2023, Номер 13(1)

Опубликована: Ноя. 27, 2023

The underlying genetic and epigenetic mechanisms driving functional adaptations in neuronal excitability excessive alcohol intake are poorly understood. Small-conductance Ca

Язык: Английский

Процитировано

5
DNA methylation of miR-181a-5p mediated by DNMT3b drives renal interstitial fibrosis developed from acute kidney injury DOI Creative Commons
Huaxi Liu,

Yijian Deng,

Guanfeng Luo

и другие.

Epigenomics, Год журнала: 2024, Номер 16(13), С. 945 - 960

Опубликована: Июль 2, 2024

Aim: To explore the role of miR-181a-5p in progression acute kidney injury (AKI) to renal interstitial fibrosis (RIF) from perspective DNA methylation. Materials & methods: The was confirmed by collecting clinical samples, injecting agomir into tail vein, and transfecting mimic vitro. mechanism miR-181a-5p's influence on AKI induced RIF investigated methylation-specific PCR, bioinformatic analysis, transcriptome sequencing so on. Results: MiR-181a-5p plays an important RIF. DNMT3b-mediated promoter hypermethylation is main reason for downregulation miR-181a-5p. HDAC9 SNAI2 are direct targets Conclusion: Hypermethylation mediated DNMT3b promotes targeting SNAI2.

Язык: Английский

Процитировано

1
The Impact of Alcohol-Induced Epigenetic Modifications in the Treatment of Alcohol use Disorders DOI
Francesca Fanfarillo, Giampiero Ferraguti, Marco Lucarelli

и другие.

Current Medicinal Chemistry, Год журнала: 2023, Номер 31(36), С. 5837 - 5855

Опубликована: Окт. 13, 2023

Alcohol use disorders are responsible for 5.9% of all death annually and 5.1% the global disease burden. It has been suggested that alcohol abuse can modify gene expression through epigenetic processes, namely DNA histone methylation, acetylation, microRNA expression. The influence on mechanisms leads to molecular adaptation a wide number brain circuits, including hypothalamus-hypophysis-adrenal axis, prefrontal cortex, mesolimbic-dopamine pathways endogenous opioid pathways. Epigenetic regulation represents an important level alcohol-induced in brain. demonstrated acute chronic exposure induce opposite modifications mechanisms: increases decreases methylation inhibits methyltransferase activity, while induces hypermethylation DNA. Some studies investigated chromatin status during withdrawal period craving showed was associated with low status, elevated activity deacetylase decreased acetylation. Given effects exerted by ethanol consumption mechanisms, structure modifiers, such as inhibitors inhibitors, might represent new potential strategy treat disorder. Further investigations induced be helpful develop therapies alcoholism drug addiction targeting processes.

Язык: Английский

Процитировано

3
Adolescent social housing protects against adult emotional and cognitive deficits and alters the PFC and NAc transcriptome in male and female C57BL/6J mice DOI Creative Commons

Jyoti Lodha,

Emily R. Brocato,

M W Nash

и другие.

Frontiers in Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Дек. 7, 2023

Introduction Adolescence is a critical period in cognitive and emotional development, characterized by high levels of social interaction increases risk-taking behavior including binge drinking. Adolescent exposure to stress ethanol have individually been associated with the development social, emotional, deficits, as well increased risk for alcohol use disorder. Disruption cortical early life and/or drinking may partly underlie these enduring cognitive, behavioral effects. The study goal implement novel neighbor housing environment identify effects adolescent on (1) battery tasks (2) adult behavior, (3) nucleus accumbens prefrontal cortex transcriptome. Methods male female C57BL/6J mice were single or housed without access intermittent ethanol. One cohort underwent testing during adulthood determine preference, expression anxiety-like performance, patterns intake. second was sacrificed late adolescence brain tissue used transcriptomics analysis. Results As adults, displayed decreased interaction, deficits object recognition task, relative neighbor-housed mice. There no effect condition consumption. did not alter Transcriptomics analysis revealed that resulted differential genes related synaptic plasticity methylation, extracellular matrix inflammation cortex. Discussion results indicate via model protect against deficits. In addition, suggest alterations be mediated part dysregulation transcription frontal accumbens.

Язык: Английский

Процитировано

2
Cross-species epigenetic regulation of nucleus accumbens KCNN3 transcripts by excessive ethanol drinking. DOI Creative Commons

Rita Cervera Juanes,

Patrick J. Mulholland,

Audrey E. Padula

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Сен. 15, 2023

The underlying genetic and epigenetic mechanisms driving functional adaptations in neuronal excitability excessive alcohol intake are poorly understood. Small-conductance Ca2+-activated K+ (KCa2 or SK) channels encoded by the KCNN family of genes have emerged from preclinical studies as a key contributor to alcohol-induced neuroadaptations alcohol-drinking monkeys dependent mice. Here, this cross-species analysis focused on KCNN3 DNA methylation, gene expression, single nucleotide polymorphisms including alternative promoters that could influence surface trafficking function KCa2 channels. Bisulfite sequencing nucleus accumbens tissue mice revealed differentially methylated region exon 1A overlaps with predicted promoter sequence. hypermethylation paralleled an increase expression transcripts encode apamin-insensitive dominant-negative channel isoforms. A polymorphic repeat macaque 1 did not correlate drinking. At protein level, KCa2.3 was significantly reduced very heavy drinking monkeys. Together, our findings dysregulation represent complex mechanism utilizes impact firing neurons. Thus, these results provide support for possible molecular harmful use disorder.

Язык: Английский

Процитировано

0