Effect of BRD4 Inhibitor on Cognitive Deficit and c-Fos /BDNF level in rats with Alzheimer's disease

This study evaluated the effect of intra-hippocampal injection of JQ1 on cognitive deficiency and protein level of c-Fos and brain-derived neurotrophic factor (BDNF) in the hippocampus of rats with Alzheimer's disease (AD). Twenty - four male Wistar rats weighing 200-250g were divided into three groups saline+DMSO, Aβ+saline+DMSO, and JQ1+Aβ+saline+DMSO. To induce AD model, 2μl of Aβ1–42 protofibrils were bilaterally injected into the CA1 of the hippocampus. JQ1 was injected into the dorsal hippocampus chronically (2μl/5μg /6 times), then rats were trained in a Y maze and stepped through passive avoidance (STP) to evaluate memory function. c-Fos and BENF were evaluated using western blotting. Data were analyzed by ANOVA one-way in SPSS software version 26. According to the results, rats receiving JQ1+Aβ+saline+DMSO (2μl/5μg of dissolved JQ1 in saline incubated at 24º C with 1% DMSO) represented 27.6% improvement in memory compared with the group of Aβ+saline+DMSO in STP ( P <0.001). Also, significant improvement in alternation behavior in the Y maze ( P =0.001), first latency, and total time spent (TTS) in the darkroom ( P =0.001) compared with Aβ+saline+DMSO group. Western blot analysis showed an increase in BDNF protein ( P =0.002), but a reduction in c-Fos protein in JQ1 treated group compared with Aβ+saline+DMSO ( P =0.020). In conclusion, the administration of JQ1 could improve memory function in the AD model of rats probably via elevating BDNF and reducing c-Fos. Graphical Abstract