Investigating the Role of Glyoxalase 1 as a Therapeutic Target for Cocaine and Oxycodone Use Disorder DOI Creative Commons

Elizabeth Alcantara,

Michelle R. Doyle, Clara A. Ortez

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 23, 2024

Abstract Methylglyoxal (MG) is an endogenously produced non-enzymatic side product of glycolysis that acts as a partial agonist at GABA A receptors. MG metabolized by the enzyme glyoxalase-1 (GLO1). Inhibition GLO1 increases methylglyoxal levels, and has been shown to modulate various behaviors, including decreasing seeking cocaine-paired cues ethanol consumption. The goal these studies was determine if inhibition could alter cocaine-or oxycodone-induced locomotor activation and/or conditioned place preference (CPP) cocaine or oxycodone. We used both pharmacological genetic manipulations address this question. Administration inhibitor s-bromobenzylglutathione cyclopentyl diester (pBBG) did not response Additionally, pBBG had no significant effect on for Genetic knockdown Glo1 , which conceptually similar inhibition, have any effects preference, nor overexpression affect cocaine. In summary, our results show neither influence CPP

Язык: Английский

Long‐term impact of obesity: Unraveling adipose epigenetic memory DOI Creative Commons
Laura C. Hinte, Daniel Castellano‐Castillo, Ferdinand von Meyenn

и другие.

Clinical and Translational Medicine, Год журнала: 2025, Номер 15(3)

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

1

A nociceptive amygdala-striatal pathway for chronic pain aversion DOI Creative Commons
Jessica A. Wojick, Alekh Paranjapye,

Juliann K. Chiu

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 13, 2024

The basolateral amygdala (BLA) is essential for assigning positive or negative valence to sensory stimuli. Noxious stimuli that cause pain are encoded by an ensemble of

Язык: Английский

Процитировано

6

A multi-omics and cell type-specific characterization of the ventral striatum in human cocaine use disorder DOI Creative Commons
Eric Zillich,

Annasara Artioli,

A.C. Rossetti

и другие.

Cell Reports, Год журнала: 2025, Номер 44(2), С. 115332 - 115332

Опубликована: Фев. 1, 2025

Epigenome, transcriptome, and proteome analyses of postmortem brains have revealed initial molecular insights into cocaine use disorder (CUD). However, the inter-relationship between these omics contribution individual cell types remains largely unknown. We present an in-depth analysis changes in ventral striatum CUD at multi-omics single-cell resolution. Integrative microRNA sequencing (microRNA-seq), RNA (RNA-seq), proteomics datasets 41 individuals single-nuclei RNA-seq a subset 16 conserved deregulation metabolic pathways, oxidative phosphorylation, glutamatergic signaling. Cell type-specific identified inverse pathway patterns glial neuronal cells, notably astrocytes medium-spiny neurons (MSNs). Characterizing astrocyte-neuron crosstalk altered cell-cell adhesion signaling CUD. By applying comprehensive analytical framework, our study provides novel CUD-associated highlighting perturbation astrocytes, MSNs, their

Язык: Английский

Процитировано

0

Epigenetic Insights into Substance Use Disorder and Associated Psychiatric Conditions DOI Creative Commons
A. Ngo,

Christopher M Ahmad,

Niki Gharavi Alkhansari

и другие.

Complex Psychiatry, Год журнала: 2025, Номер 11(1), С. 12 - 36

Опубликована: Март 3, 2025

Background: Substance use disorder (SUD) is closely associated with epigenetic modifications that significantly impact mental health outcomes. Alcohol and drug misuse induce widespread changes in the epigenome transcriptome of central nervous system, disrupting critical processes such as reward signaling emotional regulation. These alterations regulation gene expression often persist even after substance cessation, potentially contributing to onset or worsening psychiatric conditions, including schizophrenia, depression, stress, anxiety. Summary: This review delves into key mechanisms underlying SUD its comorbid disorders, a focus on DNA methylation, histone modifications, noncoding RNA Additionally, it examines influence environmental biological factors evaluates emerging epigenetic-based therapeutic strategies aimed at treating related conditions. Key Messages: Gaining deeper understanding driving disorders crucial for development effective interventions. highlights potential pharmacological mitigate societal personal burdens linked complications.

Язык: Английский

Процитировано

0

Modeling escalation of drug intake to identify molecular targets for treating substance use disorders: a slippery slope upward DOI
Michael T. Bardo,

Richard Charnigo,

Jakob D. Shaykin

и другие.

Neuroscience & Biobehavioral Reviews, Год журнала: 2025, Номер unknown, С. 106175 - 106175

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0

Substance Addiction Rehabilitation Drugs DOI Creative Commons
Shu Yuan, Sicong Jiang, Zhongwei Zhang

и другие.

Pharmaceuticals, Год журнала: 2024, Номер 17(5), С. 615 - 615

Опубликована: Май 10, 2024

The relapse rate of substance abusers is high, and addiction rehabilitation adjunct drugs need to be developed urgently. There have been numerous reports on blocking the formation addiction, but studies that can alleviate withdrawal symptoms are very limited. Both dopamine transporter (DAT) hypothesis D3 receptor (D3R) proposed. DAT activators reduce extracellular level, D3R antagonists neuron’s sensitivity dopamine, both which may exacerbate subsequently. partial agonist SK608 has biased signaling properties via G-protein-dependent pathway did not induce desensitization and, thus, a promising drug for symptoms. Drugs serotoninergic neurons or GABAergic anti-inflammatory auxiliary effects treatments. promote structural synaptic plasticity also discussed.

Язык: Английский

Процитировано

2

Breaking the Chains: Advances in Substance Addiction Research through Single-Cell Sequencing, Epigenetics, and Epitranscriptomic DOI Creative Commons
Ana Filošević, I. Matic, Lara Saftić Martinović

и другие.

Future Pharmacology, Год журнала: 2024, Номер 4(1), С. 115 - 138

Опубликована: Янв. 29, 2024

Addiction is a complex brain disease influenced by genetic, environmental, and neurological factors. Psychostimulants, cocaine, methamphetamine influence different cell types in regions, with focus on the neurons responsible for rewarding effects nucleus accumbens (NAc) ventral tegmental area (VTA). Known markers psychostimulant-induced neuronal plasticity combination droplet-based high-throughput single-cell sequencing divided heterogeneity of populations NAc VTA into clusters, where all cells same type do not respond equally to exposure psychostimulants. To explain as changes amplitude phase shifts gene expression, we focused epigenetic mechanisms DNA chromatin modifications, well accessibility. We also comment epitranscriptomics novel approach study messenger RNA posttranslational modification, which regulates translation potentially localized transcription synapses order address molecular chains that connect addiction from expression synaptic and, finally, plasticity.

Язык: Английский

Процитировано

1

Role of serotonin neurons in the dorsal raphe nucleus in heroin self-administration and punishment DOI Creative Commons
Chen Li,

Nicholas McCloskey,

Saadet Inan

и другие.

Neuropsychopharmacology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 19, 2024

Язык: Английский

Процитировано

1

Adaptive circuits for action and value information in rodent operant learning DOI Creative Commons
Alain Ríos, Kyohei Fujita, Yoshikazu Isomura

и другие.

Neuroscience Research, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

1

Construction and evaluation of a new rat reference genome assembly, GRCr8, from long reads and long-range scaffolding DOI
Kai Li, Melissa Smith, John C. Blazier

и другие.

Genome Research, Год журнала: 2024, Номер 34(11), С. 2081 - 2093

Опубликована: Ноя. 1, 2024

We report the construction and analysis of a new reference genome assembly for Rattus norvegicus , laboratory rat, widely used experimental animal model organism. The has been adopted as rat by Genome Reference Consortium is named GRCr8. employed 40× Pacific Biosciences (PacBio) HiFi sequencing coverage scaffolding using optical mapping Hi-C. genomic DNA from male BN/NHsdMcwi (BN) same strain colony prior assembly, mRatBN7.2. at chromosome level with 98.7% sequence assigned to chromosomes. All chromosomes have increased in size compared k -mer indicates that subject fully inbred represented single haploid assembly. Notable increases are observed Chromosomes 3, 11, 12 prospective rDNA regions. In addition, Chr Y threefold more consistent karyotype than previous assemblies. Several other grown incorporation sizable discrete blocks. These contain highly repetitive sequences encode numerous previously unannotated genes. centromeric incorporated most annotation performed NCBI RefSeq, which confirms improvement quality adds 1100 protein coding PacBio Iso-Seq data acquired multiple tissues released concurrently aid further analyses.

Язык: Английский

Процитировано

1