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Histone H3 dopaminylation in ventral tegmental area underlies heroin-induced maladaptive plasticity

ABSTRACT: Histone H3 dopaminylation in ventral tegmental area underlies heroin-induced maladaptive plasticity

PROVIDER: PRJNA717243 | ENA |

REPOSITORIES: ENA

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Histone H3 dopaminylation in ventral tegmental area underlies heroin-induced maladaptive plasticity

Project description:Persistent transcriptional events in ventral tegmental area (VTA) and other reward relevant brain regions contribute to enduring behavioral adaptations that characterize substance use disorder (SUD). Recent data from our laboratory indicate that aberrant accumulation of the newly discovered histone post-translational modification (PTM), H3 dopaminylation at glutamine 5 (H3Q5dop), contributes significantly to cocaine-seeking behavior following prolonged periods of abstinence. It remained unclear, however, whether this modification is important for relapse vulnerability in the context of other drugs of abuse, such as opioids. Here, we showed that H3Q5dop plays a critical role in heroin-mediated transcriptional plasticity in midbrain. In rats undergoing abstinence from heroin self-administration (SA), we found acute and persistent accumulation of H3Q5dop in VTA. By attenuating H3Q5dop during abstinence, we both altered gene expression programs associated with heroin withdrawal and reduced heroin-primed reinstatement behavior. These findings thus establish an essential role for H3Q5dop, and its downstream transcriptional consequences, in opioid-induced plasticity in VTA.

2022-02-20 | GSE169628 | GEO

RNA-sequencing in rat ventral tegmental area (VTA) following chronic ethanol and withdrawal

Project description:The objective of The Center for Alcohol Research in Epigenetics (CARE) is to identify gene regulatory pathways in ventral tegmental area (VTA) that are altered in response to chronic ethanol administration and withdrawal.

2024-02-15 | GSE233921 | GEO

Age-mediated transcriptomic changes in adult mouse brain ventral tegmental area

Project description:Substantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease. However, ventral tegmental area (VTA), a region adjacent to SNpc, is less affected in PD. Until now, molecular mechanisms behind VTA aging have not been fully investigated using high throughput techniques. Here, aging-associated early changes in transcriptome of VTA were investigated comparing late middle-aged (18 months old) to young (2 months old) mice. Three age groups of C57 wild type mice were used in microarray analysis: young (2 months old), middle aged (10 months old), and late-middle aged (18 months old) mice. Four replicates were included in each age group and each replicate was pooled from 5 mice (5 mice/replicate x 4 replicates x 3 age groups). Total RNA was isolated from VTA for hybridization on Affymetrix microarrays.

2013-05-29 | E-GEOD-45044 | biostudies-arrayexpress

Age-mediated transcriptomic changes in adult mouse brain ventral tegmental area

2013-05-29 | GSE45044 | GEO

RNA-SEQ profiling of dopaminergic neurons from the substantia nigra pars compacta and ventral tegmental area regions of the mouse mid-brain

Project description:RNA-SEQ profiling of dopaminergic neurons from the substantia nigra pars compacta and ventral tegmental area regions of the mouse mid-brain Murine midbrain dopaminergic neurons from the SNpc and VTA regions

2015-07-27 | E-GEOD-64452 | biostudies-arrayexpress

The effect of early life social stress on mouse Ventral Tegmental Area transcriptomic profile

Project description:This study investigated the impact of psychosocial stress experienced during adolescence on the development of the brain dopaminergic system. The experiment was designed to evaluate the transcriptomic changes in the ventral tegmental area of mouse brain after one week of repeated exposure to a threatening mouse during preadolescence (P14-P21).

2022-03-31 | GSE199136 | GEO

Transcription profiling of dopaminergic neurons of the substantia nigra pars compacta (SNc) and the ventral tegmental area from normal rats

Project description:The cardinal clinical features of Parkinson's disease result from selective loss of midbrain dopaminergic neurons. The goal of this experiment is to determine the gene expression profiles of these neurons by studying untreated rat substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) dopaminergic neurons using laser capture microscopy to obtain region-specific neuronal mRNA.

2007-10-27 | E-GEOD-1157 | biostudies-arrayexpress

RNA-SEQ profiling of dopaminergic neurons from the substantia nigra pars compacta and ventral tegmental area regions of the mouse mid-brain

Project description:RNA-SEQ profiling of dopaminergic neurons from the substantia nigra pars compacta and ventral tegmental area regions of the mouse mid-brain

2015-07-27 | GSE64452 | GEO

Dopaminylation of Histone H3 in Ventral Tegmental Area Regulates Cocaine-seeking

Project description:Vulnerability to relapse during periods of attempted abstinence from cocaine use is hypothesized to result from rewiring of brain reward circuitries, particularly ventral tegmental area (VTA) dopamine neurons. How cocaine exposures act on midbrain dopamine neurons to precipitate addiction-relevant changes in gene expression is unclear. We found that histone H3 glutamine 5 dopaminylation (H3Q5dop) plays a critical role in cocaine-induced transcriptional plasticity in midbrain. Rats undergoing withdrawal from cocaine showed an accumulation of H3Q5dop in VTA. By reducing H3Q5dop in VTA during withdrawal, we reversed cocaine-mediated gene expression changes, attenuated cue-induced dopamine release in nucleus accumbens and reduced cocaine-seeking behavior. These findings establish a neurotransmission-independent role for nuclear dopamine in relapse-related transcriptional plasticity in VTA.

2020-05-19 | GSE124055 | GEO

Adult rat ventral tegmental area single-nucleus RNA-seq dataset for "An atlas of transcriptionally defined cell populations in the rat ventral tegmental area"

Project description:Adult rat ventral tegmental area single-nucleus RNA-seq dataset for "An atlas of transcriptionally defined cell populations in the rat ventral tegmental area"

| PRJNA706368 | ENA

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