Expression changes in the prefrontal cortex after neurotransmission blocking of nucleus accumbens pathways
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PROVIDER: PRJNA512534 | ENA |
REPOSITORIES: ENA
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Project description:Animal models provide opportunity to study neurobiological aspects of human alcoholism. Changes in gene expression have been implicated in mediating brain function, including reward system and addiction. The current study aimed to identify novel genes that may underlie ethanol preference. Microarray analysis comparing gene expression in nucleus accumbens (NAc), hippocampus (HP) and prefrontal medial cortex (mPFC) was performed in two rat strains selected for extreme levels of ethanol preference - Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP). The identified candidate genes may underlie differential ethanol preference in rat model of alcoholism. This is analysis of 18 RNA samples, including 9 technical replicates. Two strains of rats selected for extreme levels of ethanol preference (low preferring WLP and high preferring WHP) were compared. Three brain areas (nucleus accumbens, prefrontal medial cortex and hippocampus) were studied. For each brain area, 6 RNA samples (including 3 technical replicates) were analyzed. Each RNA sample consist of of equal amounts of total RNA from 3 male rats. Comparisons: Nucleus accumbens of WHP vs. Nucleus accumbens of WLP; Prefrontal medial cortex of WHP vs. Prefrontal medial cortex of WLP; Hippocampus of WHP vs. Hippocampus of WLP. 3 biological replicates in each comparison.
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Project description:We applied next-generation sequencing to analyse changes in the expression of Dclk1 gene isoforms in the brain in response to several psychoactive drugs with diverse pharmacological mechanisms of action. We used bioinformatics tools to define the range and levels of Dclk1 transcriptional regulation in the mouse nucleus accumbens and prefrontal cortex
2018-07-17 | GSE117174 | GEO
Project description:Transcriptional alterations in dorsolateral prefrontal cortex and nucleus accumbens implicate neuroinflammation and synaptic remodeling in opioid use disorder. Transcriptomic profile of 20 control subjects and 20 OUD subjects in brain region DLPFC and NAC
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Project description:Chronic jet lag (CJL) induced by shifting light-dark cycles repeatedly is a commonly used protocol to mimic the environmental light/dark changes encountered by shift workers. We conducted RNA sequencing using prefrontal cortex (PFC) and nucleus accumbens (NAc) tissues from these animals, which are brains regions strongly implicated in the pathology of various neurological and psychiatric conditions. Our results reveal the alterations of brain activities and systematic reprogramming of gene expression in brain tissues under CJL, building hypothesis for how CJL increases the susceptibility to neurological and psychiatric diseases.
2020-10-01 | GSE153540 | GEO
Project description:Catechol-O-methyltransferase (COMT) is an ubiquitously expressed enzyme that maintains basic biologic functions by inactivating catechol substrates. In humans, polymorphic variance at the COMT locus has been associated with modulation of pain sensitivity (Andersen & Skorpen, 2009) and risk for developing psychiatric disorders (Harrison & Tunbridge, 2008). A functional haplotype associated with increased pain sensitivity was shown to result in decreased COMT activity by altering mRNA secondary structure-dependent protein translation (Nackley et al., 2006). However, the exact mechanisms whereby COMT modulates pain sensitivity and behavior remain unclear and can be further studied in animal models. We have pursued a genome-wide approach to examining gene expression in multiple brain regions in inbred strains of mice and have discovered that Comt1 is differentially expressed. This expression difference was validated with qPCR. A B2-B4 Short Interspersed Element (SINE) was inserted in the 3'UTR of Comt1 in 14 strains that also shared a common haplotype. Experiments using mammalian expression vectors of full-length cDNA clones with and without the SINE element demonstrate that strains with the SINE haplotype (+SINE) have greater Comt1 enzymatic activity. +SINE mice also exhibit behavioral differences in anxiety assays and decreased pain sensitivity. These results suggest that a haplotype, defined by a 3'UTR B2-B4 SINE element, regulates Comt1 expression and mouse behavior. Brain region samples were isolated from male and female mice of 29 strains (n = 3), 129S1/SvImJ, A/J, AKR/J, BALB/cByJ, BTBR T+ tf/J, BUB/BnJ , C3H/HeJ, C57BL/6J, C57BR/cdJ, C58/J, CBA/J, CE/J, DBA/2J, FVB/NJ, I/LnJ, KK/HIJ, MA/MyJ, MRL/MpJ, NOD/LtJ, NON/LtJ, NZO/HILTJ, NZW/LacJ, P/J, PL/J, RIIIS/J, SJL/J, SM/J, SWR/J, and WSB/EiJ. Eight to ten week old male and female mice of each strain were purchased from the Jackson Laboratory (Bar Harbor, ME, USA). The mice were habituated for one week prior to tissue collection. Mice were sacrificed by cervical dislocation without anesthesia to avoid gene expression differences in response to anesthetic. All dissections were conducted between the hours of 9:00AM to 11:30AM. Prefrontal cortex and nucleus accumbens were dissected as follows. Immediately following euthanasia, mice were decapitated and the whole brain was removed from the skull. The brain was then transferred, ventral side up, to an ice-cold brain matrix with 0.5mm spacing (505C Braintree Scientific). A single razor blade was placed into the first space on the brain matrix and the rostral surface of the brain was placed in the matrix and touching this blade. Thin, double-edged razor blades were placed in the twelve most anterior spaces. Following removal from the matrix, the 0.5 mm brain slices were placed flat onto an ice-cold dissection stage and specific regions dissected using anatomical landmarks as described below. The prefrontal cortex was taken from the slice corresponding to approximately 2.5 mm to 2.0 mm anterior to Bregma. To do so, a V-shaped wedge was made just medial to the corpus callosum with the apex terminating at about the lateral ventricle (viewed from the caudal side of the slice). Nucleus accumbens was taken from the adjacent slice approximately 2.0mm to 1.5mm anterior to Bregma. To isolate nucleus accumbens, 1mm punches were taken just ventromedial to the anterior commissure. All of the array data in this Series are from male mice.
2010-02-23 | E-GEOD-20160 | biostudies-arrayexpress
Project description:This article presents a study that examines the proteomic alterations associated with opioid use disorder (OUD) in the human brain. The study investigates the interplay between pro-inflammatory signaling, extracellular matrix (ECM) remodeling, and synaptic plasticity in the corticostriatal circuitry associated with OUD. The findings reveal differential alterations in the synaptic proteomes across the nucleus accumbens (NAc) and dorsolateral prefrontal cortex (DLPFC), indicating that changes in certain synaptic subtypes are unique to each brain region. The proteomic alterations associated with OUD in DLPFC are mainly in glutamatergic, serotonergic, dopaminergic, and oxytocin signaling, while altered adrenergic signaling is enriched in NAc. The study also identifies alterations in proteins involved in circadian entrainment specifically in synaptic enrichments in both DLPFC and NAc of OUD subjects. These findings provide new evidence linking disrupted molecular rhythms in the regulation of distinct synaptic subtypes altered by opioids.
2023-10-25 | PXD041333 | Pride
Project description:Enduring patterns of epigenomic and transcriptional plasticity within the mesolimbic dopamine system contribute importantly to persistent behavioral adaptations that characterize substance use disorders (SUD). While drug addiction has long been thought of as a disorder of dopamine (DA) neurotransmission, therapeutic interventions targeting receptor mediated DA-signaling have not yet resulted in efficacious treatments. Our laboratory recently identified a non-canonical, neurotransmission-independent signaling moiety for DA in brain, termed dopaminylation, whereby DA itself acts as a donor source for the establishment of post-translational modifications (PTM) on substrate proteins (e.g., histone H3 at glutamine 5; H3Q5dop). In our previous studies, we demonstrated that H3Q5dop plays a critical role in the regulation of neuronal transcription and, when perturbed within monoaminergic neurons of the ventral tegmental area (VTA), critically contribute to pathological states, including relapse vulnerability to both psychostimulants (e.g., cocaine) and opiates (e.g., heroin). Importantly, H3Q5dop is also observed throughout the mesolimbic DA reward pathway (e.g., in nucleus accumbens/NAc and medial prefrontal cortex/mPFC, which receive DA input from VTA). As such, we investigated whether H3Q5dop may similarly be altered in its expression in response to drugs of abuse in these non-dopamine-producing regions. In rats undergoing extended abstinence from cocaine self-administration (SA), we observed both acute and prolonged accumulation of H3Q5dop in NAc, but not mPFC. Attenuation of H3Q5dop in NAc during drug abstinence reduced cocaine-seeking and affected cocaine-induced gene expression programs associated with altered dopamine signaling and neuronal function. These findings thus establish H3Q5dop in NAc, but not mPFC, as an important mediator of cocaine-induced behavioral and transcriptional plasticity during extended cocaine abstinence.
2023-06-14 | GSE221177 | GEO
Project description:Alcohol use disorder (AUD) has a profound public health impact and understanding of the molecular mechanisms underlying the development and progression of AUD remain limited. Many genetic risk loci have been identified for AUD or alcohol consumption, though the neurobiological mechanisms underlying these loci remain largely unknown. DNA methylation (DNAm) differences between individuals with and without AUD can provide insight into the mechanisms that predispose to AUD and consequences of AUD itself. Here, we provide Illumina HumanMethylation EPIC array data generated in nucleus accumbens and dorsolateral prefrontal cortex, both addiction relevant brain tissues, from 119 decedents of European ancestry: 61 controls and 58 cases. From these data we have conducted an epigenome-wide association study (EWAS) and identified several CpG associations with AUD. A subset of the identified CpGs map to genes that were previoulsy identified as associated with substance use behaviors in genetic studies, but the other CpGs map to genes previoulsy unassociated with substance use behaviors and are novel.
2024-01-18 | GSE252501 | GEO
Project description:Animal models provide opportunity to study neurobiological aspects of human alcoholism. Changes in gene expression have been implicated in mediating brain function, including reward system and addiction. The current study aimed to identify novel genes that may underlie ethanol preference. Microarray analysis comparing gene expression in nucleus accumbens (NAc), hippocampus (HP) and prefrontal medial cortex (mPFC) was performed in two rat strains selected for extreme levels of ethanol preference - Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP). The identified candidate genes may underlie differential ethanol preference in rat model of alcoholism. This study was supported through funding from the following grants: Polish Scientific Committee Grant 2011/03/N/NZ29/05222, Polish Ministry of Science and Higher Education Grants “Iuventus Plus” (IP2011 030371) and N N519 657940.
2015-01-17 | GSE65064 | GEO