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Caroline Holtkamp, Björn Koos, Matthias Unterberg, Tim Rahmel, Lars Bergmann, Zainab Bazzi, Maha Bazzi, Hassan Bukhari, Michael Adamzik, Katharina Rump

• \(\bf Background\) Propofol is a widely used anaesthetic drug with advantageous operating conditions and recovery profile. However, propofol could have long term effects on neuronal cells and is associated with post-operative delirium (POD). In this context, one of the contributing factors to the pathogenesis of POD is a reduction of cholinesterase activity. Accordingly, we investigated the effects of propofol on the methylation, expression and activity of cholinergic genes and proteins in an \(\it in-vitro\) model. \(\bf Results\) We found that propofol indeed reduced the activity of AChE / BChE in our \(\it in-vitro\) model, without affecting the protein levels. Furthermore, we could show that propofol reduced the methylation of a repressor region of the CHRNA7 gene without changing the secretion of pro–or anti-inflammatory cytokines. Lastly, propofol changed the expression patterns of genes responsible for maintaining the epigenetic status of the cell and accordingly reduced the tri-methylation of H3 K27. \(\bf Conclusion\) In conclusion we found a possible functional link between propofol treatment and POD, due to a reduced cholinergic activity. In addition to this, propofol changed the expression of different maintenance genes of the epigenome that also affected histone methylation. Thus, propofol treatment may also induce strong, long lasting changes in the brain by potentially altering the epigenetic landscape.