Mechanism of high frequency rTMS on cognitive function in cerebral ischemic rats based on RNA sequencing

Abstract

Objective: To clarify the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on cognitive function in cerebral ischemic rats, and to explore its underlying mechanism by RNA sequencing. Methods: Thirty male Sprague-Dawley (SD) rats underwent transient middle cerebral artery occlusion (tMCAO). According to the Bederson score, 10 rats with a score of 1-3 were excluded, and the remaining 20 rats were then randomly divided into the tMCAO group (n=10) and the rTMS group (n=10). Meanwhile, 10 rats with sham operation were assigned to the sham group (n=10). Rats in the rTMS group received 20 Hz rTMS from day 7 to day 28 after surgery. From day 28 to day 33 after the operation, Morris water maze test was performed to detect the cognitive function of rats in each group. The cortical tissues around the infarcts from the rTMS tMCAO groups were taken for RNA sequencing analysis, with 3 rats in each group. Results: The escape latency of rats in the rTMS group[ (53±4)s] and the group [(51±5)s] were significantly shorter than that of the tMCAO group[ (58±4)s, P<0.05)]. The times that the rats crossed the original platform in 60 seconds in the rTMS group[2.5 (1.5-3.0)] and sham group[3.0 (1.5-3.0)] were more than that of the tMCAO group [1.0(0.5-1.5)] (P<0.05). RNA sequencing detected 16 significantly differentially expressed genes, including 9 up-regulated genes and 7 down-regulated genes. GO analysis showed that the functions of up-regulated genes were mainly concentrated in the processes of chemical homeostasis and cell metal ion homeostasis. While the functions of down-regulated genes mainly enriched in the inflammatory response. Conclusion: Twenty Hz rTMS can improve the cognitive function of rats with cerebral infarction, and its underlying mechanism may be related to maintaining chemical and metal ion homeostasis and regulating the polarization of microglia to reduce neuroinflammation.