Transcriptional effects of low-dose methamphetamine treatment on the mouse hippocampus

In this study, we constructed a mouse model of methamphetamine addiction. We administered 2 mg/kg methamphetamine to C57Bl/6 mice 4 times at 1-day intervals. Behavioral tests revealed cognitive memory impairment in METH-addicted mice. Transcriptional analysis showed significant downregulation of the neural progenitor/stem cell markers Sox2 and Nes among the differentially expressed genes, as well as qPCR results of hippocampal tissue identical to the sequencing results, suggesting that METH may have led to reduced proliferation of hippocampal neural progenitor cells and impaired adult hippocampal neurogenesis. We explored the effects of METH on adult hippocampal neurogenesis and the ameliorative effects of exercise and overexpression of beta-catenin on METH-induced injury. We found that exercise ameliorates METH-induced reduction in hippocampal neurogenesis and cognitive memory impairment through the GSK3b/beta-catenin pathway, providing meaningful suggestions for pathogenic mechanisms and more effective potential therapeutic avenues for methamphetamine neurotoxicity injury.Experimental design: Male C57BL/6 mice were injected intraperitoneally with methamphetamine dissolved in sterile saline four times at 1-day intervals. Control mice were injected with sterile saline at the same time. At the end of the experiment, RNA was extracted from the isolated hippocampus and analyzed by mRNA sequencing.