To gauge a better understanding, the team also wanted to investigate how illicit drugs affected class II HDAC protein levels and HAT expression. These HDACs (HDACs 4, 5, 6, & 7) play a role in neural signaling pathways and response to environmental stimuli, and epigenetic changes due to drug exposure have yet to be studied in depth.
Cocaine and METH exposure were found to increase HDAC4, HDAC6, and HDAC7 levels, while decreasing HDAC5 levels. Morphine exposure increased only HDAC4 levels but downregulated the other HDACs. These are significant findings because HDAC4 is known to play an important role in memory and spatial learning, as well as some movement functions, while increased levels of HDAC6 have been linked to mood disorders and depression. The drug/Piracetam combination was found to help bring HDAC levels close to the control.
Overall, the researchers found that these drugs had more of an impact on class II HDACs than on class I HDACs.
To determine the effect the drugs had on HAT expression, the team used the p300 Polyclonal Antibody and the Histone H3 Acetylation Antibody Panel Pack I in a western blot analysis against the astrocytes. They found that METH and cocaine had significantly upregulated p300 levels, but downregulated other HAT proteins GCN5 and PCAF. Morphine exposure decreased GCN5 levels slightly, but not significantly. When each drug was paired with Piracetam, each of the HAT proteins returned to close to the control levels, again indicating the potential benefit of Piracetam.
The drugs studied in this paper are some of the most addictive and abused drugs in the world. The findings highlight the epigenetic damage that happens to the human nervous system due to the continued use of these drugs, but there may be some promise for neuroprotection found in nootropic drugs like Piracetam. Each HDAC and HAT protein levels can impact different parts of neurodevelopment and behavior, making these discoveries critical for understanding the effects that psychostimulants and opioids have on human cells. Dr. Thangavel and his team hope to continue to expand their research to see which specific HAT and HDACs affect acetylation levels in the presence of illicit drugs.
Doke M, Pendyala G, Samikkannu T (2021) Psychostimulants and opioids differentially influence the epigenetic modification of histone acetyltransferase and histone deacetylase in astrocytes. PLoS ONE 16(6)
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