Neuroprotective Effect of Piracetam against Cocaine-Induced Neuro Epigenetic Modification of DNA Methylation in Astrocytes

Abstract

Cocaine abuse is known to alter mitochondrial biogenesis and induce epigenetic modification linked with neuronal dysfunction. Cocaine-induced epigenetic modification of DNA methylation and the mitochondrial genome may affect mitochondrial DNA (mtDNA) and nuclear DNA (nDNA), as epigenetic DNA methylation is key to maintaining genomic integrity in the central nervous system (CNS). However, the impact of cocaine-mediated epigenetic changes in astrocytes has not yet been elucidated. In this study, we explored the neuroprotective effect of piracetam against cocaine-induced epigenetic changes in DNA methylation in astrocytes. To study our hypothesis, we exposed human astrocytes to cocaine alone or in combination with the nootropic drug piracetam. We examined the expression of the DNA methyltransferases (DNMTs) DNMT-1, DNMT-3A, and DNMT-3B; global DNA methylation levels of 5-methycytosine (5-mC); and induction of ten–eleven translocation (TET) enzymes in astrocytes. In addition, we analyzed mtDNA methylation by targeted next-generation bisulfite sequencing. Our data provide evidence that cocaine impairs DNMT activity and thereby has impacts on mtDNA, which might contribute to the neurodegeneration observed in cocaine users. These effects might be at least partially prevented by piracetam, allowing neuronal function to be maintained.

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

“…Piracetam, cocaine, METH and morphine were prepared in cell culture-grade distilled water to obtain working concentrations. To investigate the effects of cocaine, METH, morphine and piracetam, the cultured cells were divided into eight groups: (i) control cells exposed to media alone, (ii) piracetam (10 μM), (iii) cocaine (1 μM), (iv) piracetam and cocaine, (v) METH (10 μM), (vi) piracetam and METH, (vii) morphine (5 μM), and (viii) piracetam and morphine for 24 h. The doses used in this study were based from our previous published studies [36][37][38][39]. Cocaine (1 μM), METH (10 μM), morphine (5 μM) and piracetam (10 μM) did not show any toxicity at particular mentioned concentrations.…”

Reproductive Potential Impacts Body Maintenance Parameters and Global DNA Methylation in Honeybee Workers (Apis mellifera L.)

“…Biostimulants and herbs reduce the level of global DNA methylation, while pesticides, acaricides, and other anthropogenic factors increase it at a certain age stage of bees [18][19][20]49,[52][53][54]. In other organisms, i.e., Osmia rufa [55], Varroa destructor [56], human [57,58], the level of global DNA methylation is much higher than in A. mellifera workers. In turn, social hymenopterans, such as wasps, and ants, have low levels of DNA methylation [59][60][61].…”

HIV-1 Tat and cocaine impact astrocytic energy reservoirs and epigenetic regulation by influencing the LINC01133-hsa-miR-4726-5p-NDUFA9 axis

“…To investigate the effects of HIV-1 Tat and cocaine on cultured cells, we divided the cells into four groups: (1) control cells exposed to medium alone, (2) cells treated with HIV-1 Tat (50 ng/mL), (3) cells exposed to cocaine (1 μM), and (4) cells exposed to HIV-1 Tat (50 ng/mL) and cocaine (1 μM) (TC) in combination for 24 h. The optimized doses and times used in the present studies were based on our published report. 62 , 76 …”