How omics is revealing new roles for glia in addiction

Glia, Journal Year: 2024, Volume and Issue: 73(3), P. 608 - 618

Published: June 18, 2024

Experiments to study the biology of addiction have historically focused on mechanisms through which drugs abuse drive changes in functioning neurons and neural circuits. Glia often been ignored these studies, however, this has left many questions field unanswered, particularly, surrounding how glia contribute synaptic plasticity, regulation neuroinflammation, ensembles given massive signaling across CNS. Omics methods (transcriptomics, translatomics, epigenomics, proteomics, metabolomics, others) expanded researchers' abilities generate hypotheses carry out mechanistic studies glial cells during acquisition drug taking, intoxication, withdrawal, relapse seeking. Here, we present a survey omics technological advances are revising our understanding astrocytes, microglia, oligodendrocytes, ependymal biology.

Language: Английский

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Dopamine and dopamine receptor D1 as a novel favourable biomarker for hepatocellular carcinoma

Cancer Cell International, Journal Year: 2021, Volume and Issue: 21(1)

Published: Oct. 30, 2021

Abstract Background Hepatocellular carcinoma (HCC) remains one of the most common malignant tumours worldwide. Therefore, identification and development sensitivity- genes as novel diagnostic markers effective therapeutic targets is urgently needed. Dopamine dopamine receptor D1 (DRD1) are reported to be involved in progression various cancers. However, crucial role DRD1 HCC activities unclear. Methods We enrolled 371 patients with liver hepatocellular (LIHC) from The Cancer Genome Atlas (TCGA) detect expression functions DRD1. Tumour Immune Estimation Resource (TIMER), UALCAN database, Kaplan–Meier plotter, cBioPortal LinkedOmics database were utilized for systematic investigation related clinical features, coexpressed genes, functional pathways, mutations, immune infiltrates HCC. Results In this study, we determined that was decreased tumour tissues versus normal low indicated a poor prognosis. significance varied among different samples. somatic mutation frequency LIHC cohort 0.3%. biological detected validated, shown activities, including metabolism, oxidation, mitochondrial matrix-related processes other signaling pathways. addition, out study had significant correlations infiltration macrophages, B cells CD+ T Conclusions These findings demonstrated rationality potential application function biomarker diagnosis target treatment.

Language: Английский

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Addiction-like behaviour towards high-fat high-sugar food predicts relapse propensity in both obesity prone and obesity resistant C57BL/6 J mice

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2022, Volume and Issue: 121, P. 110654 - 110654

Published: Oct. 6, 2022

Language: Английский

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Heightened cocaine-seeking in male rats associates with a distinct transcriptomic profile in the medial prefrontal cortex

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 14, 2022

Drug overdose deaths involving cocaine have skyrocketed, an outcome attributable in part to the lack of FDA-approved medications for treatment use disorder (CUD), highlighting need identify new pharmacotherapeutic targets. Vulnerability cocaine-associated environmental contexts and stimuli serves as a risk factor relapse CUD recovery, with individual differences evident motivational aspects these cues. The medial prefrontal cortex (mPFC) provides top-down control striatal circuitry regulate incentive-motivational properties stimuli. Clinical preclinical studies identified genetic variations that impact degree executive restraint over drug-motivated behaviors, we designed present study employ next-generation sequencing specific genes associated heightened cue-evoked cocaine-seeking mPFC male, outbred rats. Rats were trained stably self-administer cocaine, baseline cue-reinforced was established. phenotyped either high cue (HC) or low (LC) responders based upon lever pressing previously cues allowed 10 days abstinence their home cages prior collection RNA-sequencing. expression 309 significantly different HC vs. LC Functional gene enrichment analyses ten biological processes overrepresented identifies distinctions mRNA transcripts characterizes relapse-like behavior prioritized candidates future pharmacotherapeutics aimed help maintain CUD. In particular Htr2c gene, which encodes serotonin 5-HT 2C receptor (5-HT R), is expressed lower extent rats, relative These findings build on plethora previous also point R attractive target

Language: Английский

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Regulator of G-Protein Signalling 9: A New Candidate Gene for Sweet Food Liking?

Foods, Journal Year: 2023, Volume and Issue: 12(9), P. 1739 - 1739

Published: April 22, 2023

Genetics plays an important role in individual differences food liking, which influences choices and health. Sweet liking is a complex trait has been associated with increased body mass index (BMI) related comorbidities. This genome-wide association study (GWAS) aimed to investigate the genetics of sweet using two adult discovery cohorts (n = 1109, n 373) independent replication cohort 1073). In addition, we tested our strongest result on parameters behaviour (food adventurousness (FA) reward dependence (RD) health status (BMI blood glucose). The results demonstrate novel strong between Regulator G-Protein Signalling 9 (RGS9I) gene, single nucleotide polymorphism (SNP) rs58931966 (p-value 7.05 × 10-9 combined sample replication), minor allele (A) being decreased liking. We also found that A SNP was FA RD, BMI glucose (p-values < 0.05). Differences were highlighted sex-specific analysis glucose. Our highlight genetic are indicative variation influencing psychological-biological drivers preference. If confirmed other studies, such associations could allow greater understanding chronic disease management from both habitual dietary intake reward-related perspective.

Language: Английский

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Orphan peptide and G protein‐coupled receptor signalling in alcohol use disorder

British Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 181(5), P. 595 - 609

Published: Dec. 11, 2023

Neuropeptides and G protein-coupled receptors (GPCRs) have long been, continue to be, one of the most popular target classes for drug discovery in CNS disorders, including alcohol use disorder (AUD). Yet, orphaned neuropeptide systems (oGPCR), which no known cognate receptor or ligand, remain understudied development. Orphan neuropeptides oGPCRs are abundantly expressed within brain represent an unprecedented opportunity address function may hold potential as novel treatments disease. Here, we describe current literature regarding implicated AUD. Specifically, this review, focus on cocaine- amphetamine-regulated transcript (CART), several that been directly AUD (GPR6, GPR26, GPR88, GPR139, GPR158) discuss their pitfalls treatments, progress identifying ligands.

Language: Английский

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Differential transcriptome profile underlying risky choice in a rat gambling task

Journal of Behavioral Addictions, Journal Year: 2022, Volume and Issue: 11(3), P. 845 - 857

Published: Sept. 12, 2022

Proper measurement of expected risk is important for making rational decisions, and maladaptive decision may underlie various psychiatric disorders. However, differentially expressed genetic profiling involved in this process still largely unknown. A rodent version the gambling task (rGT) has been developed to measure decision-making by adopting same principle Iowa Gambling Task humans. In present study, we examined using next-generation sequencing (NGS) technique whether there are differences gene expression profiles medial prefrontal cortex (mPFC) nucleus accumbens (NAc) when rats make different choices toward rGT.Rats were trained a touch screen chamber learn relationships between 4 light signals on window accompanied reward outcomes or punishments set up with magnitudes probabilities. Once they showed stabilized pattern preference upon free choice, classified into risk-averse risk-seeking groups. After performing rGT, decapitated, mPFC NAc was dissected out, NGS performed total RNA extracted.We found that 477 36 genes (approximately 75 83% out them downregulated) NAc, respectively, compared rats. Among those, suggested few top ranked contribute promoting risky choices.Our findings provide insights transcriptional components underlying

Language: Английский

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THC exposure during adolescence increases impulsivity-like behavior in adulthood in a WIN 55,212-2 self-administration mouse model

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: May 25, 2023

Background Cannabis addiction is a chronically relapsing disorder lacking effective treatment. Regular cannabis consumption typically begins during adolescence, and this early cannabinoid exposure may increase the risk for drug in adulthood. Objective This study investigates development of addiction-like behavior adult mice after adolescent to main psychoactive component cannabis, Δ 9 -tetrahydrocannabinol (THC). Methods Adolescent male were exposed 5 mg/kg THC from postnatal days 37 57. Operant self-administration sessions WIN 55,212-2 (12.5 μg/kg/infusion) conducted 10 days. Mice tested three criteria (persistence response, motivation, compulsivity), two parameters related craving (resistance extinction drug-seeking behavior), phenotypic vulnerability traits substance use disorders (impulsivity reward sensitivity). Additionally, qPCR assays performed detect differentially expressed genes medial prefrontal cortex (mPFC), nucleus accumbens (NAc), dorsal striatum, hippocampus (HPC) “addicted” “non-addicted” mice. Results did not modify reinforcement nor behavior. Inversely, pre-exposed displayed impulsive-like adulthood, which was more pronounced that developed criteria. Moreover, downregulated drd2 adora2a gene expression NAc HPC revealed mice, as well downregulation mPFC vehicle pre-treated behaviors. Discussion These findings suggest promote impulsivity-like associated with HPC.

Language: Английский

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Fine-Regional Role of the Claustrum in Anxiety and Higher Sensitivity to Cocaine in Adolescent Cocaine-Exposed Male Mice during Adulthood

Journal of Neuroscience, Journal Year: 2023, Volume and Issue: 44(5), P. e0884232023 - e0884232023

Published: Dec. 26, 2023

Adolescent cocaine exposure (ACE) induces anxiety and higher sensitivity to substances abuse during adulthood. Here, we show that the claustrum is crucial for controlling these psychiatric problems in male mice. In anxiety-like behavioral tests, CaMKII-positive neurons median portion of ( M Claustrum) were triggered, local suppression reduced behavior ACE mice contrast, anterior A more activated response subthreshold dose induced conditioned place preference (CPP), blocked acquisition CPP Our findings first time identified fine-regional role regulating susceptibility adulthood, extending our understanding substance use disorder.

Language: Английский

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How life events may confer vulnerability to addiction: the role of epigenetics

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Sept. 18, 2024

Substance use disorder (SUD) represents a large and growing global health problem. Despite the strong addictive potency of drugs abuse, only minority those exposed develop SUDs. While certain life experiences (e.g., childhood trauma) may increase subsequent vulnerability to SUDs, mechanisms underlying these effects are not yet well understood. Given chronic relapsing nature length time that can elapse between prior events drug exposure, changes in SUD almost certainly involve long-term epigenetic dysregulation. To validate this idea, functional specific modifications brain regions mediating reinforcement learning nucleus accumbens, prefrontal cortex) have been investigated variety animal models In addition, produced by on studied, but mostly correlational manner. Here, we review how impact SUD-related behavior summarize our understanding relationships among experiences, regulation, future variations study design, most consistently affect produce predominantly unidirectional gene such as DNA methylation histone phosphorylation. Evidence explicitly linking environmentally induced is surprisingly sparse. We conclude offering several directions for research begin address critical gap.

Language: Английский

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