Neurotoxicity in Psychostimulant and Opiate Addiction

Niedzielska, Ewa; Rospond, Bartłomiej; Pomierny-Chamioło, Lucyna; Sadakierska‐Chudy, Anna; Filip, Małgorzata

doi:10.1007/978-1-4614-5836-4_179

Cited by 2 publications

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“…and 3F. Interestingly, coexposure to morphine and piracetam restored the protein levels of GCN5 compared to those in the control, as shown in Fig 3C.Additionally, we investigated the effect of METH on HAT protein levels and observed that METH significantly upregulated p300 levels (F(7,14) = 91.85, P = 0.0001); on the other hand, METH significantly downregulated GCN5 (F (7, 14) = 15.99, P = 0.0210) and PCAF (F (7, 14) = 52.45, P = 0.0001) levels compared to those in the control, as shown in Fig 3B-3E, 3C-3F and 3A-3D. We analyzed to compare the groups between cocaine Vs cocaine + piracetam (NS), METH Vs METH + piracetam (NS) and morphine Vs morphine + piracetam (F (7, 14) = 52.45, P <0.0001) for PCAF.…”

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confidence: 81%

“…The psychostimulants and opioid mainly affect the CNS by disrupting the brain’s cellular function, therefore affecting decision making and can cause memory dysfunction [ 6 ]. Additionally, psychostimulants and opioid can induce oxidative stress, energy metabolism and epigenetic modifications [ 7 ]. Furthermore, these drugs disrupt complex interactions in the brain linked to astrocytes that engage in crosstalk with neurons.…”

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confidence: 99%

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Psychostimulants and opioids differentially influence the epigenetic modification of histone acetyltransferase and histone deacetylase in astrocytes

2021

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Illicit drugs are known to affect central nervous system (CNS). Majorly psychostimulants such as cocaine, methamphetamine (METH) and opioids such as morphine are known to induce epigenetic changes of histone modifications and chromatin remodeling which are mediated by histone acetyltransferase (HAT) and histone deacetylase (HDAC). Aberrant changes in histone acetylation-deacetylation process further exacerbate dysregulation of gene expression and protein modification which has been linked with neuronal impairments including memory formation and synaptic plasticity. In CNS, astrocytes play a pivotal role in cellular homeostasis. However, the impact of psychostimulants and opioid mediated epigenetic changes of HAT/HADCs in astrocytes has not yet been fully elucidated. Therefore, we have investigated the effects of the psychostimulants and opioid on the acetylation-regulating enzymes- HAT and HDACs role in astrocytes. In this study, Class I and II HDACs and HATs gene expression, protein changes and global level changes of acetylation of H3 histones at specific lysines were analyzed. In addition, we have explored the neuroprotective “nootropic” drug piracetam were exposed with or without psychostimulants and opioid in the human primary astrocytes. Results revealed that psychostimulants and opioid upregulated HDAC1, HDAC4 and p300 expression, while HDAC5 and GCN5 expression were downregulated. These effects were reversed by piracetam coexposure. Psychostimulants and opioid exposure upregulated global acetylation levels of all H3Ks, except H3K14. These results suggest that psychostimulants and opioids differentially influence HATs and HDACs.

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confidence: 81%

Section: Introductionmentioning

confidence: 99%

Psychostimulants and opioids differentially influence the epigenetic modification of histone acetyltransferase and histone deacetylase in astrocytes

2021

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Influence of psychostimulants and opioids on epigenetic modification of class III histone deacetylase (HDAC)-sirtuins in glial cells

Sivalingam

Doke

Khan

et al. 2021

Sci Rep

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Substance abuse affects the central nervous system (CNS) and remains a global health problem. Psychostimulants, such as cocaine and methamphetamine (METH), and opioids affect neuronal function and lead to behavioral impairments via epigenetic modification. Epigenetic changes occur via classical pathways, especially the class III histone deacetylase (HDAC)-sirtuin (SIRT) family, that act as cellular sensors to regulate energy homeostasis and coordinate cellular responses to maintain genome integrity. However, SIRT family (1–7)-associated neurodegeneration has not been elucidated in the context of energy metabolism. The present study examined the effects of psychostimulants, such as cocaine and METH, and opioids, such as morphine, on SIRT family (1–7) [class I, II, III and IV] expression and cellular translocation-mediated dysfunction in astrocytes and microglial cells. The “nootropic” drug piracetam played a preventative role against psychostimulant- and opioid-induced SIRT (1–7) expression in astrocytes. These results indicate that cocaine, METH, and morphine affected deacetylation and cellular function, and these changes were prevented by piracetam in astrocytes.

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Neurotoxicity in Psychostimulant and Opiate Addiction

Cited by 2 publications

References 357 publications

Psychostimulants and opioids differentially influence the epigenetic modification of histone acetyltransferase and histone deacetylase in astrocytes

Psychostimulants and opioids differentially influence the epigenetic modification of histone acetyltransferase and histone deacetylase in astrocytes

Influence of psychostimulants and opioids on epigenetic modification of class III histone deacetylase (HDAC)-sirtuins in glial cells

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