Effects of RG2833 (HDAC1/3 Inhibitor) on the gene expression of Female TgF344 Alzheimer’s disease Rat model.

We investigated the long-term therapeutic effects of oral administration of a brain-penetrant HDAC1/3 inhibitor RG2833 in a Fisher transgenic 344-AD (TgF344-AD) rats model of AD. We treated for 6 months, starting at 5 months of age administering the drug in rodent chow at ~30mg/kg of body weight. After treatment we performed experiements to show the effects of drug treatment on spatial memory deficits. We show significantly improved hippocampal-dependent spatial memory performance in TgF344-AD female. To investigate the effect of RG2833 on hippocampal gene expression, we have 5 (chow treated rats) TgF344 and 5 (RG2833 chow treated) rats. At 11 months of age, the rats were anaesthetized intraperitoneally with ketamine (100 mg/kg) and xylazine (10 mg/kg) and transcardially perfused with cold RNAse-free 1× PBS. Left hippocampi were removed and snap frozen for RNAseq analysis. Left hemisphere of the hippocampus. F1 – F5 (untreated transgenic rats), FRG1 – FRG5 (transgenic AD rats treated with the drug RG2833). Female Rats started RG2833 treatment at 5-months of age and were treated for 6 months untli they were 11 months old. ). For this experiment, the gene expression for the drug treated transgenic rats will be compared to that of the untreated transgenic group (FRG/F)