Benefits of diazoxide/dibenozylmethane (DZ/DIB) co-treatment on hippocampal gene expression in Female Fisher transgenic 344-AD rats.. Benefits of diazoxide/dibenozylmethane (DZ/DIB) co-treatment on hippocampal gene expression in Female Fisher transgenic 344-AD rats.

Alzheimer’s disease (AD) is the major cause of dementia prevalent in older adults and with a high incidence in females; thus, Identification of early biomarkers is important for preventive interventions. To show potential early biomarkers, we carried out RNA-Sequencing analysis for 4-month(pre-pathology) TgF344-AD rats, a transgenic Alzheimer’s model that exhibits age-dependent AD progression. Our study showed two potential early biomarker genes (early growth response 2 (EGR2) and histone H2AA (HISIT1H2AA)) for AD, in the hippocampus of 4-month TgF344-AD females compared to wild-type littermates. Furthermore, due to the multifactorial cause for AD, we tested the therapeutic benefit of a multi-target approach using a co-treatment with diazoxide (DZ), a potassium channel activator, and dibenzoylmethane (DIB), which inhibits eIF2α-P activity, on TgF344-AD female. Our results strongly support the DZ/DIB-treatment as potential strategy to mitigate AD pathology due to its multi-target approach. Overall design: To show the potential early hippocampal biomarker gene expression. Hippocampi of Five (4-month-old) TgF344-AD rats and Five (4-month-old) Wild-type female rats were analyzed for gene expression by RNAseq To show the effects of diazoxide/dibenozylmethane (DZ/DIB) co-treatment on gene expression levels, Hippocampi of Six (4-month old) TgF344-AD DZ/DIB -treated rats and Four (4-month old) untreated TgF344-AD Female rats were analyzed for gene expression by RNAseq At 4 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. For DZ/DIB treated rats, treatment began at age (52 days) and ended at 4-month. WT1 – WT5 (Untreated Wild-type rats), Tg1 – Tg5 (Untreated transgenic AD rats); Tg-1- Tg-5 (Untreated transgenic AD rats) and Tg-C1-Tg-C6 (transgenic AD rats treated with the drugs diazoxide and dibenozylmethane) For the early biomarker experiment, the gene expression for the transgenic rats was compared to that of the Wild-type group (Tg1-5/WT1-5). For the effects of DZ/DIB, the gene expression for the DZ/DIB treated rats was compared to that of the untreated transgenic rats (Tg-C1-6/ Tg-1-5) *************************************************************** submitter states that fastq files are no longer available. ***************************************************************