Epigenetic mechanisms involved in methamphetamine addiction

Wang, Hang; Dong, Xianghuan; Awan, Maher Un Nisa; Bai, Jie

doi:10.3389/fphar.2022.984997

Cited by 7 publications

(7 citation statements)

References 74 publications

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“…2,3 METH disrupts the normal neuronal activity in the brain by enhancing the release of neurotransmitters such as dopamine, serotonin, and glutamate. 4 Prolonged methamphetamine abuse is associated with neuronal loss in various brain regions, including the substantia nigra pars compacta and locus coeruleus, resulting in the deterioration of different cognitive domains, including memory and decision-making. [5][6][7] Kami et al reported that repetitive METH treatment impairs working memory through suppression of the ERK1/2 pathway in the hippocampus.…”

Section: Introductionmentioning

confidence: 99%

“…Adverse consequences resulting from its abuse have emerged as a worldwide concern, 2 as it impairs the functionality and cognitive processes of the central nervous system (CNS) 2,3 . METH disrupts the normal neuronal activity in the brain by enhancing the release of neurotransmitters such as dopamine, serotonin, and glutamate 4 . Prolonged methamphetamine abuse is associated with neuronal loss in various brain regions, including the substantia nigra pars compacta and locus coeruleus, resulting in the deterioration of different cognitive domains, including memory and decision‐making 5–7 .…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal stem cell‐derived exosomes improve neurogenesis and cognitive function of mice with methamphetamine addiction: A novel treatment approach

Fallahi,

Zangbar,

Farajdokht

et al. 2024

CNS Neurosci Ther

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BackgroundMethamphetamine (METH) is a psychostimulant substance with highly addictive and neurotoxic effects, but no ideal treatment option exists to improve METH‐induced neurocognitive deficits. Recently, mesenchymal stem cells (MSCs)‐derived exosomes have raised many hopes for treating neurodegenerative sequela of brain disorders. This study aimed to determine the therapeutic potential of MSCs‐derived exosomes on cognitive function and neurogenesis of METH‐addicted rodents.MethodsMale BALB/c mice were subjected to chronic METH addiction, followed by intravenous administration of bone marrow MSCs‐derived exosomes. Then, the spatial memory and recognition memory of animals were assessed by the Barnes maze and the novel object recognition test (NORT). The neurogenesis‐related factors, including NeuN and DCX, and the expression of Iba‐1, a microglial activation marker, were assessed in the hippocampus by immunofluorescence staining. Also, the expression of inflammatory cytokines, including TNF‐α and NF‐κB, were evaluated by western blotting.ResultsThe results showed that BMSCs‐exosomes improved the time spent in the target quadrant and correct‐to‐wrong relative time in the Barnes maze. Also, NORT's discrimination index (DI) and recognition index (RI) were improved following exosome therapy. Additionally, exosome therapy significantly increased the expression of NeuN and DCX in the hippocampus while decreasing the expression of inflammatory cytokines, including TNF‐α and NF‐κB. Besides, BMSC‐exosomes down‐regulated the expression of Iba‐1.ConclusionOur findings indicate that BMSC‐exosomes mitigated METH‐caused cognitive dysfunction by improving neurogenesis and inhibiting neuroinflammation in the hippocampus.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell‐derived exosomes improve neurogenesis and cognitive function of mice with methamphetamine addiction: A novel treatment approach

Fallahi,

Zangbar,

Farajdokht

et al. 2024

CNS Neurosci Ther

View full text Add to dashboard Cite

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“…METH is another commonly abused psychostimulant that induces synaptic plasticity and pathological memory enhancement [61]. Epigenetics plays an important role in regulating METH addiction [62]. METH modulates dopamine (DA), norepinephrine (NE), serotonin, glutamate (Glu), and GABA neurotransmitters in the medial prefrontal cortex (mPFC), the VTA, and the NAc through histone acetylation, methylation, micro RNAs (miR-NAs), and ubiquitination.…”

Section: Identifying Cell Populations By Molecular Clusteringmentioning

confidence: 99%

Breaking the Chains: Advances in Substance Addiction Research through Single-Cell Sequencing, Epigenetics, and Epitranscriptomic

Filošević Vujnović,

Stanković Matić,

Saftić Martinović

et al. 2024

Future Pharmacology

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Addiction is a complex brain disease influenced by genetic, environmental, and neurological factors. Psychostimulants, cocaine, and methamphetamine influence different cell types in different brain regions, with a focus on the neurons responsible for rewarding effects in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Known markers for psychostimulant-induced neuronal plasticity in combination with droplet-based high-throughput single-cell sequencing divided the heterogeneity of cell populations in NAc and VTA into clusters, where all cells of the same type do not respond equally to exposure to psychostimulants. To explain psychostimulant-induced neuronal plasticity as changes in the amplitude and phase shifts of gene expression, we focused on epigenetic mechanisms of DNA and chromatin modifications, as well as DNA accessibility. We also comment on epitranscriptomics as a novel approach in the study of messenger RNA posttranslational modification, which regulates translation and potentially localized transcription in synapses in order to address the molecular chains that connect addiction from changes in gene expression to synaptic and, finally, neuronal plasticity.

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“…DNA methylation has also been shown to be an important gene regulatory mechanism for MA-induced alterations in learning and memory in mouse models 20 . Epigenetics plays an important role in regulating MA addiction 21 . However, few studies have reported about its association with MAUD-related psychotic symptoms.…”

Section: Introductionmentioning

confidence: 99%

Association of single nucleotide polymorphism and methylation of dopamine system-related genes with psychotic symptoms in patients of methamphetamine use disorders

Fang

Liu

et al. 2023

Preprint

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Background: Methamphetamine use disorders (MAUD) can substantially jeopardize public security due to their high-risk social psychology and behavior. Given that the dopamine reward system is intimately associated with MAUD, we investigated the association of single nucleotide polymorphisms (SNPs), as well as methylation status of DRD4, COMT genes and paranoid, motor impulsive symptoms in MAUD patients. Methods: A total of 189 MAUD patients participated in our study. Samples of peripheral blood were used to detecte for 3 SNPs and levels of 35 CpG units of methylation in the DRD4 gene’s promoter region, 5 SNPs and 39 CpG units in the COMT gene. Results: MAUD patients with rs1800955 C allele have a lower percentage of paranoid symptom than those with rs1800955 TT. Individuals with paranoid symptom exhibited reduced methylation degree at particular DRD4 CpG2.3 unit. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4 CpG2.3 methylation degree resulted in the lower occurrence of the paranoid symptom. Meanwhile, those with COMT rs4818 CC allele have lower motor impulsivity scores in MAUD patients, but greater COMT methylation levels in the promotor region and methylation degree at COMT CpG 51.52 unit. Therefore, based only on COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor impulsivity scores in the MAUD patients. Conclusions: Our results found that the combination of SNP genotyping and methylation status of the DRD4 and COMT genes may serve as biological indicators to evaluate the prevalence of relatively high-risk psychotic symptoms in MAUD patients.

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Epigenetic mechanisms involved in methamphetamine addiction

Cited by 7 publications

References 74 publications

Mesenchymal stem cell‐derived exosomes improve neurogenesis and cognitive function of mice with methamphetamine addiction: A novel treatment approach

Mesenchymal stem cell‐derived exosomes improve neurogenesis and cognitive function of mice with methamphetamine addiction: A novel treatment approach

Breaking the Chains: Advances in Substance Addiction Research through Single-Cell Sequencing, Epigenetics, and Epitranscriptomic

Association of single nucleotide polymorphism and methylation of dopamine system-related genes with psychotic symptoms in patients of methamphetamine use disorders

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