Astrocytic transcriptional and epigenetic mechanisms of drug addiction

Holt, Leanne M.; Nestler, Eric J.

doi:10.1007/s00702-023-02716-4

Cited by 3 publications

(4 citation statements)

References 192 publications

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“…More recently, observations of changes in gene expression mediated by transcriptional and epigenetic regulations brought about by drugs have provided fresh venues for potential therapeutic interventions. In this regard, evidence of robust transcriptional response of astrocytes to several substances of abuse, whereby astrocytes are directly implicated in drug seeking behaviors has been provided [185].…”

Section: Astrocytes -Drug Addictionmentioning

confidence: 99%

Role of Glial Cells in Depression and Drug Addiction

Tizabi,

Getachew,

Hauser

et al. 2024

Preprint

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Major depressive disorder (MDD) and substance use disorder (SUD) are of immense medical and social concerns. Although significant progress on neuronal involvement in mood and reward circuitries has been achieved, only relatively recently the role of glia in these disorders have attracted attention. Detail understanding of the glial function in these devastating diseases could offer novel interventions. Here, following a brief review of circuitries involved in mood regulation and reward perception, specific contribution of the neurotrophic factors, neuroinflammation and gut microbiota to these diseases are highlighted. In this context, the role of specific glial cells (e.g., microglia, astroglia, oligodendrocytes and synantocytes) on phenotypic manifestation of MDD or SUD are emphasized. In addition, potential use of this knowledge in developing novel therapeutics is touched upon.

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Section: Astrocytes -Drug Addictionmentioning

confidence: 99%

Role of Glial Cells in Depression and Drug Addiction

Tizabi,

Getachew,

Hauser

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…More recently, observations of changes in gene expression, mediated by transcriptional and epigenetic regulations brought about by drugs, have provided fresh venues for potential therapeutic interventions. In this regard, evidence of the robust transcriptional response of astrocytes to several substances of abuse, whereby astrocytes are directly implicated in drug seeking behaviors, has been provided [203][204][205].…”

Section: Astrocytes-drug Addictionmentioning

confidence: 99%

Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction

Tizabi,

Getachew,

Hauser

et al. 2024

Brain Sciences

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Mood disorders and substance use disorder (SUD) are of immense medical and social concern. Although significant progress on neuronal involvement in mood and reward circuitries has been achieved, it is only relatively recently that the role of glia in these disorders has attracted attention. Detailed understanding of the glial functions in these devastating diseases could offer novel interventions. Here, following a brief review of circuitries involved in mood regulation and reward perception, the specific contributions of neurotrophic factors, neuroinflammation, and gut microbiota to these diseases are highlighted. In this context, the role of specific glial cells (e.g., microglia, astroglia, oligodendrocytes, and synantocytes) on phenotypic manifestation of mood disorders or SUD are emphasized. In addition, use of this knowledge in the potential development of novel therapeutics is touched upon.

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“…Given the well known dopamine and glutamate hypotheses in schizophrenia (37,38) and the replicated microglial density reductions (Translocator Protein 18 kDa, TSPO) (39), our primary hypothesis was that regional MAO-B V T is reduced in rst-episode psychosis (FEP) patients and CHR individuals compared to healthy volunteers (HV). Furthermore, given the pre-clinical evidence of reduced GFAP expression and astrocytic alterations (32,40) and decreased in-vitro MAO-B expression (41,42) in response to cannabis or delta-9-tetrahydrocannabinol (THC) exposure, we expected lower MAO-B V T with cannabis use. We also predicted that the group and cannabis effect on MAO-B V T will differ between regions, given the varying MAO-B density across brain regions (35) and region-speci c striatal alterations in psychosis (43).…”

Section: Introductionmentioning

confidence: 98%

“…Moreover, reduced platelet MAO-B activity has been reported in the peripheral tissues of individuals with schizophrenia, although its relation to central MAO-B is debated (see review (30)). Nevertheless, tobacco smoking among patients in these prior investigations was a major confounder, due to both MAO-B binding (31) and astrocyte inhibitory chemicals present in cigarette smoke (32). To date, the status of MAO-B in living brains of patients with psychosis is unknown.…”

Section: Introductionmentioning

confidence: 99%

Evidence of Altered Monoamine Oxidase B, an Astroglia Marker, in Early Psychosis with Cannabis Use

Aji,

Lalang,

Ramos-Jiménez

et al. 2024

Preprint

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A novel radiotracer, [11C]SL25.1188 targets monoamine oxidase-B (MAO-B) enzyme, which metabolizes monoamines (including dopamine) primarily found in astrocytes. Altered astrocyte function in schizophrenia is supported by convergent evidence from post-mortem, genetic, transcriptomic, peripheral and preclinical findings. However, this has never been tested in living brains of early psychosis. Thirty-eight participants including antipsychotic-free/minimally exposed patients with first-episode psychosis (FEP), clinical high-risk (CHR) individuals and healthy volunteers (HVs) underwent a 90-minute positron emission tomography (PET) scan with [11C]SL25.1188, to measure MAO-B VT, an index of MAO-B concentration. Participants were excluded if tested positive on urine drug screen (except for cannabis). This study of 14 FEP (mean[SD] age, 25.7[5.7] years; 6 F), 7 CHR (mean[SD] age, 20.9[3.7] years; 4 F) and 17 HV (mean[SD] age, 31.2[13.9] years; 9 F) demonstrated significant group differences in regional MAO-B VT (F(2,37.46) = 4.56, p = 0.02, Cohen’s f = 0.49), controlling for tobacco (F (1,37.46) = 5.50 p = 0.02) and cannabis use (F(1,37.46) = 5.05, p = 0.03) with significant reductions in CHR compared to HV (Cohen’s d = 0.99). We report a significant cannabis effect on MAO-B VT (F(1,39.47) = 12.45, p = 0.001, Cohen’s f = 0.56), with a significant group-by-cannabis interaction (F(2,37.35) = 3.81, p = 0.03, Cohen’s f = 0.45), indicating lower MAO-B VT in cannabis-using patients. Decreased MAO-B VT levels was more robust in striatal than cortical regions, in both clinical groups (F(12,46.07) = 2.00, p = 0.046, Cohen’s f = 0.72) and in cannabis users (F(6,46.07) = 6.01, p < 0.001, Cohen’s f = 0.89). Reduced MAO-B concentration supports astrocyte dysfunction in cannabis-using CHR and FEP patients. Reduced MAO-B is consistent with replicated striatal dopamine elevation in psychosis, as well as astrocyte dysfunction in schizophrenia.

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Astrocytic transcriptional and epigenetic mechanisms of drug addiction

Cited by 3 publications

References 192 publications

Role of Glial Cells in Depression and Drug Addiction

Role of Glial Cells in Depression and Drug Addiction

Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction

Evidence of Altered Monoamine Oxidase B, an Astroglia Marker, in Early Psychosis with Cannabis Use

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