mRNA-Seq of the CA1 hippocampal subregion from 3 month old animals injected with JQ1 (50mg/kg) i.p. and mRNA-Seq of CA1 of 8-10 month old APP/PS1-21 transgenic animals injected with JQ1 (50mg/kg) i.p.. Mus musculus

Histone acetylation is essential for memory formation and provides a drug target to treat dementia. The histone acetylation landscape is shaped by chromatin writer and eraser proteins. In contrast, little is known about the neural activity of chromatin readers that link chromatin state to cellular function. Here, we tested the effect of JQ1 – a small molecule inhibitor of the chromatin readers BRD2, BRD3, BRD4 and BRDT – on associative and spatial memory tasks and on synaptic plasticity and found that it is able to enhance cognitive performance and long-term potentiation in wildtype animals and in a mouse model for amyloid deposition. JQ1 elicited a hippocampal gene expression program associated with ion channel activity, transcription and DNA repair. Our findings suggest that JQ1 could be used as a therapy against dementia and should be further tested in the context of learning and memory. Overall design: mRNA profile from the CA1 hippocampal subregion from adult (3 month old) WT and aged (8-10 month old) APP/PS1-21 animals treated with 50mg/kg JQ1 i.p. for 10-13 days