Effects of ibudilast treatment on hippocampal gene expression in Female Fisher transgenic 344-AD rats.

5 month old Female Fisher transgenic 344-AD (Tg-AD) rats expressing humanSwedishamyloid precursor protein (APPsw) and ? exon 9 presenelin-1 (PS1?E9) were treated with Ibudilast (cat. no. HY-B0763, MCE) at 10 mg/kg body weight administered in rodent chow. Following 6 months of Ibudilast treatment, rats (11 months of age) were tested for cognitive behaviour prior to sacrificing. Hippocampal Brain region were dissected and RNA sequencing (RNAseq) analyses was done on the Isolated sample. Taken together we showed that Ibudilast treatment: (i) reduces inflammation by decreasing the levels of the pro inflammatory cytokine IL6, interferon receptor 1, the macrophage migration inhibitory factor (MIF), microglial associated proteins such as transmembrane protein 119 (TMEM119), arachidonate 5-lipoxygenase activating protein (Alox5ap), toll like receptor 7 (TLR7), lysosomal protein transmembrane 5 (LAPTM5) and triggering receptor expressed on myeloid cells 2 (TREM2); (ii) increases expression of synaptic proteins such as synaptotagmin 2 (SYT2), which regulates vesicular transport, syntaxins (STX), which participates in neurotransmitter release, and cadherin (CDH1), which maintains synapse structure; and (iii) reduces the expression of the neurotrophic factor BDNF by 2-fold in both male and female treated rats. Overall design: To show the effects of ibudilast-treatment on gene expression levels, Hippocampi of 5 Ibudilast -treated and 5 untreated transgenic rats of Female rats were analysed for gene expression by RNAseq 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), FIB1 – FIB5 (transgenic AD rats treated with the drug ibudilast). Female Rats started ibudilast treatments at 5-months of age and were treated for 6 months until 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 (FIB1-5/F1-5) Male and Female Data uploaded separately. Male data have been assigned GEO accession numbers (GSE245214)