Sex differences in anxiety and depression: circuits and mechanisms

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(11), P. 674 - 684

Published: Sept. 20, 2021

Language: Английский

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Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models

Science Advances, Journal Year: 2023, Volume and Issue: 9(6)

Published: Feb. 10, 2023

Cocaine use disorder (CUD) is an intractable syndrome, and rising overdose death rates represent a substantial public health crisis that exacts tremendous personal financial costs on patients society. Sharp increases in cocaine drive the urgent need for better mechanistic insight into this chronic relapsing brain currently lacks effective treatment options. To investigate transcriptomic changes involved, we conducted RNA sequencing two striatal regions are heavily implicated CUD, nucleus accumbens caudate nucleus, from men suffering CUD matched controls. Weighted gene coexpression analyses identified CUD-specific networks enriched ionotropic receptors linked to lowered neuroinflammation, contrasting proinflammatory responses found opioid disorder. Integration of comprehensive datasets mouse self-administration models revealed evolutionarily conserved implicate especially D1 medium spiny neurons as drivers cocaine-induced plasticity.

Language: Английский

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Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 31, 2024

Abstract In brain, the striatum is a heterogenous region involved in reward and goal-directed behaviors. Striatal dysfunction linked to psychiatric disorders, including opioid use disorder (OUD). subregions are divided based on neuroanatomy, each with unique roles OUD. OUD, dorsal altered processing, formation of habits, development negative affect during withdrawal. Using single nuclei RNA-sequencing, we identified both canonical (e.g., dopamine receptor subtype) less abundant cell populations interneurons) human striatum. Pathways related neurodegeneration, interferon response, DNA damage were significantly enriched striatal neurons individuals markers also elevated opioid-exposed rhesus macaques. Sex-specific molecular differences glial subtypes associated chronic stress found particularly female individuals. Together, describe different types identify type-specific alterations

Language: Английский

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Transcriptional signatures of heroin intake and relapse throughout the brain reward circuitry in male mice

Science Advances, Journal Year: 2023, Volume and Issue: 9(23)

Published: June 9, 2023

Opioid use disorder (OUD) looms as one of the most severe medical crises facing society. More effective therapeutics will require a deeper understanding molecular changes supporting drug-taking and relapse. Here, we develop brain reward circuit-wide atlas opioid-induced transcriptional regulation by combining RNA sequencing (RNA-seq) heroin self-administration in male mice modeling multiple OUD-relevant conditions: acute exposure, chronic intake, context-induced drug-seeking following abstinence, Bioinformatics analysis this rich dataset identified numerous patterns regulation, with both region-specific pan-circuit biological domains affected heroin. Integration RNA-seq data behavioral outcomes uncovered processes that predispose to OUD vulnerability. Comparisons human genome-wide association study revealed convergent abnormalities gene candidates high therapeutic potential. These studies outline reprogramming underlying provide foundational resource for future investigations into mechanisms treatment strategies.

Language: Английский

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Microglia in neuroimmunopharmacology and drug addiction

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(6), P. 1912 - 1924

Published: Feb. 2, 2024

Language: Английский

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Opioid-driven disruption of the septal complex reveals a role for neurotensin-expressing neurons in withdrawal

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

Published: Jan. 16, 2024

Because opioid withdrawal is an intensely aversive experience, persons with use disorder (OUD) often relapse to avoid it. The lateral septum (LS) a forebrain structure that important in aversion processing, and previous studies have linked the substance disorders. It unclear, however, which precise LS cell types might contribute maladaptive state of withdrawal. To address this, we used single-nucleus RNA-sequencing interrogate type specific gene expression changes induced by chronic morphine We discovered globally disrupted transcriptional profile types, but Neurotensin-expressing neurons (

Language: Английский

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Cocaine and morphine induce shared and divergent transcriptional regulation in nucleus accumbens D1 and D2 medium spiny neurons

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

Published: April 5, 2025

Language: Английский

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Single nucleus transcriptomic analysis of rat nucleus accumbens reveals cell type-specific patterns of gene expression associated with volitional morphine intake

Translational Psychiatry, Journal Year: 2022, Volume and Issue: 12(1)

Published: Sept. 8, 2022

Abstract Opioid exposure is known to cause transcriptomic changes in the nucleus accumbens (NAc). However, no studies date have investigated cell type-specific associated with volitional opioid taking. Here, we use single RNA sequencing (snRNAseq) comprehensively characterize alterations of NAc transcriptome rats self-administering morphine. One cohort male Brown Norway was injected acute morphine (10 mg/kg, i.p.) or saline. A second allowed self-administer intravenous (1.0 mg/kg/infusion) for 10 consecutive days. Each morphine-experienced rat paired a yoked saline control rat. snRNAseq libraries were generated from punches and used identify gene expression We identified 1106 differentially expressed genes (DEGs) group, compared 2453 DEGs self-administration across 27 distinct clusters. Importantly, 1329 that specific self-administration. novel clusters astrocytes, oligodendrocytes, D1R- D2R-expressing medium spiny neurons NAc. Cell included Rgs9 , Celf5 Oprm1 Pde10a . Upregulation validated by RNAscope. Approximately 85% all oligodendrocyte DEGs, nearly which taking, two subtypes. Bioinformatic analyses upstream regulatory mechanisms observed downstream signaling pathways, including both previously molecular pathways. These findings show taking highlight striatal populations substrates could be targeted reduce compulsive

Language: Английский

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Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 28, 2023

Abstract Opioid use disorder (OUD) is influenced by genetic and environmental factors. While recent research suggests epigenetic disturbances in OUD, this mostly limited to DNA methylation (5mC). hydroxymethylation (5hmC) has been widely understudied. We conducted a multi-omics profiling of OUD male cohort, integrating neuronal-specific 5mC 5hmC as well gene expression profiles from human postmortem orbitofrontal cortex (OUD = 12; non-OUD 26). Single locus methylomic analysis co-methylation showed higher number OUD-associated genes networks for compared 5mC; these were enriched GPCR, Wnt, neurogenesis, opioid signaling. marks also correlation with patterns GWAS psychiatric traits. Drug interaction revealed interactions opioid-related drugs, some used treatments. Our findings suggest an important role reveal loci epigenetically dysregulated OFC neurons individuals OUD.

Language: Английский

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Neuroimmune Mechanisms of Opioid Use Disorder and Recovery: Translatability to Human Studies, and Future Research Directions

Neuroscience, Journal Year: 2023, Volume and Issue: 528, P. 102 - 116

Published: Aug. 9, 2023

Language: Английский

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