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Cannabinoid modulation of gene and microRNA expression in brain (basal ganglia) during chronic HIV/SIV infection

ABSTRACT: Cannabinoid modulation of gene and microRNA expression in brain (basal ganglia) during chronic HIV/SIV infection

PROVIDER: PRJNA911312 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19991183_1.fastq.gz	Fastqsanger.gz
	SRR19991183_2.fastq.gz	Fastqsanger.gz
	SRR19991184_1.fastq.gz	Fastqsanger.gz
	SRR19991184_2.fastq.gz	Fastqsanger.gz
	SRR19991185_1.fastq.gz	Fastqsanger.gz

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MicroRNA profiling of Basal ganglia tissue from chronically SIV infected rhesus macaques II

Project description:The study describes miRNA expression changes in basal ganglia (BG) of chronically SIV-infected rhesus macaques. HIV/SIV-associated neurological disorder (HAND) represents a major comorbidity affecting HIV patients on anti-retroviral therapy. Employing a systems biology approach, we report molecular changes underlying HAND and its modulation by phytocannabinoids [delta-9-tetrahydrocannabinol (9-THC)] in uninfected and SIV-infected rhesus macaques (RMs) treated with vehicle (VEH/SIV) or 9-THC (THC/SIV). VEH/SIV but not THC/SIV RMs showed significant enrichment of genes linked to anti-viral defense, interferon-beta, NFkB, RIG-1, and JAK-STAT signaling. We focused on the anti-endoplasmic reticulum (WFS1) and anti-oxidative stress (CRYM) proteins that were significantly downregulated in BG of VEH/SIV RMs. Both proteins localized to the BG neurons, and showed differential expression in the BG of THC/SIV and VEH/SIV RMs. Additionally, inflammation-associated miR-155 and miR-142-3p showed significantly higher expression in the BG of VEH/SIV RMs. In human primary HCN2 neuronal cells, miR-142-3p post-transcriptionally downregulated WFS1. These findings strongly support a role for differential miRNA expression associated with HIV/SIV induced neurological dysfunction.

2023-02-28 | GSE220709 | GEO

Transcriptome profiling of Basal ganglia tissue from chronically SIV infected rhesus macaques

Project description:Transcriptome profiling of Basal ganglia tissue from chronically SIV infected rhesus macaques

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Cannabinoid modulation of gene and microRNA expression in brain (basal ganglia) during chronic HIV/SIV infection

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-02-28 | GSE220783 | GEO

MicroRNA profiling of Basal ganglia tissue from chronically SIV infected rhesus macaques II

Project description:MicroRNA profiling of Basal ganglia tissue from chronically SIV infected rhesus macaques II

| PRJNA911219 | ENA

Transcriptome profiling of Basal ganglia tissue from chronically SIV infected rhesus macaques

Project description:The dysregulation of the microbiota-gut-brain axis (MGBA) in people living with HIV (PLWH) consequent to gastrointestinal dysfunction (dysbiosis) can lead to neuroinflammation and persistent cognitive impairment, which underscores the need for new treatments. Here, we show that delta-9-tetrahydrocannabinol (THC) reduced neuroinflammation and microbiome alterations and enhanced plasma endocannabinoid, endocannabinoid-like and indole-3-propionate levels in chronically SIV-infected rhesus macaques. Long-term low-dose THC potently blocked expression of genes associated with type I interferon responses and excitotoxicity (SLC7A11) and enhanced protein expression of WFS1 (endoplasmic reticulum stress) and CRYM (oxidative stress) in basal ganglia. Additionally, THC successfully countered miR-142-3p mediated suppression of WFS1 via a CB1R mediated mechanism in HCN2 neuronal cells. Most importantly, THC increased the relative abundance of Firmicutes and Clostridia including IPA producersing C. botulinum, C. paraputrificum, C. cadaveris and butyrate producersing C. butyricum, Faecalibacterium prauzsnitzii and Butyricicoccus pullicaecorum in the colon. This study highlights low-dose THC as a potential disease-modifying agent that can positively modulate the MGBA by concurrently reducing neuroinflammation and promoting the growth of gut microbial species that produce neuroprotective metabolites like indole-3-propionate in PLWH HIV and other neurodegenerative diseases, thus meriting clinical trials.

2023-02-28 | GSE207518 | GEO

Functional Identification of Specialized Basal Ganglia Circuits that Regulate Vocal Motor Sequences

Project description:Production of learned vocalizations requires precise selection and accurate sequencing of appropriate vocal-motor actions. The basal ganglia are essential for the selection and sequencing of motor actions, but the cellular specializations and circuit mechanisms governing accurate sequencing of vocalizations are unknown. Here, we use single-nucleus RNA sequencing and genetic manipulations to map basal ganglia cell types and circuits involved in the production of songbird vocal sequences. We identify cell-type specializations in direct-like and indirect-like basal ganglia pathways, including evolutionary expansion of striatal and arkypallidal cell-types that could facilitate vocal sequencing. We also reversibly reduced the expression of FoxP2 with a viral knockdown. For birds in which FoxP2 was knocked down, striatal neurons exhibited decreased expression of Drd1 and showed an increased ratio of Drd2/Drd1 expression. These findings identify key evolutionary specializations and circuits essential for selection and sequencing of vocal-motor actions necessary for vocal communication.

2021-05-19 | GSE136086 | GEO

Δ9-tetrahydrocannabinol (Δ9-THC) promotes neuroimmune-modulatory microRNA profile in striatum of simian immunodeficiency virus (SIV)-infected macaques.

Project description:Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Δ9-THC (THC/SIV) was profiled using next generation deep sequencing.

2016-01-22 | GSE72766 | GEO

Prospects for cannabinoid therapies in basal ganglia disorders.

Project description:Cannabinoids are promising medicines to slow down disease progression in neurodegenerative disorders including Parkinson's disease (PD) and Huntington's disease (HD), two of the most important disorders affecting the basal ganglia. Two pharmacological profiles have been proposed for cannabinoids being effective in these disorders. On the one hand, cannabinoids like Δ(9) -tetrahydrocannabinol or cannabidiol protect nigral or striatal neurons in experimental models of both disorders, in which oxidative injury is a prominent cytotoxic mechanism. This effect could be exerted, at least in part, through mechanisms independent of CB(1) and CB(2) receptors and involving the control of endogenous antioxidant defences. On the other hand, the activation of CB(2) receptors leads to a slower progression of neurodegeneration in both disorders. This effect would be exerted by limiting the toxicity of microglial cells for neurons and, in particular, by reducing the generation of proinflammatory factors. It is important to mention that CB(2) receptors have been identified in the healthy brain, mainly in glial elements and, to a lesser extent, in certain subpopulations of neurons, and that they are dramatically up-regulated in response to damaging stimuli, which supports the idea that the cannabinoid system behaves as an endogenous neuroprotective system. This CB(2) receptor up-regulation has been found in many neurodegenerative disorders including HD and PD, which supports the beneficial effects found for CB(2) receptor agonists in both disorders. In conclusion, the evidence reported so far supports that those cannabinoids having antioxidant properties and/or capability to activate CB(2) receptors may represent promising therapeutic agents in HD and PD, thus deserving a prompt clinical evaluation.

| S-EPMC3165947 | biostudies-literature

Weighted gene co-expression network analysis on microarray data from subregions of zebra finch (Taeniopygia guttata) basal ganglia

Project description:Similarities between speech and birdsong make songbirds advantageous for investigating the neurogenetics of learned vocal communication; a complex phenotype likely supported by ensembles of interacting genes in cortico-basal ganglia pathways of both species. To date, only FoxP2 has been identified as critical to both speech and birdsong. We performed weighted gene co-expression network analysis on microarray data from singing zebra finches to discover gene ensembles regulated during vocal behavior. We found ~2,000 singing- regulated genes comprising 3 co-expression groups unique to area X, the basal ganglia subregion dedicated to learned vocal-motor behavior. These contained known targets of human FOXP2 and potential avian targets. We validated novel biological pathways for vocalization. Our findings show that higher-order gene co-expression patterns, rather than expression levels, molecularly distinguish area X from the ventral striato-pallidum during singing. The previously unknown structure of singing-driven networks enables prioritization of molecular interactors that likely bear on human motor disorders, especially those affecting speech. Gene expression was measured in 2 basal ganglia sub-regions (area X & ventral striato-pallidum (VSP)) of 27 adult male zebra finches that sang different amounts of song over a 2hr period in the morning. 18 birds were allowed to sing freely, 9 birds were discouraged from singing by the presence of an investigator and those that sang fewer than 10 song motifs were considered “non-singers”.

2012-01-04 | E-GEOD-34819 | biostudies-arrayexpress

Transgenic tools targeting striatal and pallidal subpopulations reveal both evolutionary conservation and specialization of cortico-basal ganglia circuits in zebrafish

Project description:The cortico-basal ganglia circuit mediates decision-making. Here, we generated transgenic tools for adult zebrafish targeting specific subpopulations of the components of this circuit and utilized them to identify evolutionary homologs of the mammalian direct- and indirect-pathway striatal neurons which respectively project to the homologs of the internal and external segment of the globus pallidus (dEN and Vl) as in mammals. Unlike in mammals, the Vl mainly projected to the dEN directly, not by way of the subthalamic nucleus. Further single-cell RNA sequencing analysis revealed two pallidal output pathways: a major shortcut pathway directly connecting the dEN with the pallium and the evolutionarily conserved closed loop by way of the thalamus. Our resources and circuit map provide the common basis for the functional study of the basal ganglia in a small and optically tractable zebrafish brain for the comprehensive mechanistic understanding of the cortico-basal ganglia circuit.

2024-02-05 | GSE254980 | GEO

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