The novel miR_146-Tfdp2 axis antagonizes METH induced neuron apoptosis and cell cycle abnormalities in tree shrew.

Methamphetamine (METH) is a synthetic drug with potent addictive, relapse, and neurotoxic properties. METH abuse contributes to severe damage to the central nervous system, potentially causing cognitive impairments, behavioral changes, and neurodegenerative diseases. METH-induced neuronal damage is closely related to apoptosis and cell cycle abnormalities, while gene expression regulator microRNAs (miRNAs) may play extensive roles in this progress, but the specific mechanisms remain unclear. We found that the novel miRNA 146 (miR_146) was downregulated in METH-induced apoptosis and cell cycle arrest in tree shrew primary neurons, while the expression of its target gene Tfdp2 was increased after METH exposure. Overexpression of miR_146 or silencing of Tfdp2 significantly alleviated METH-induced cell cycle arrest and apoptosis in primary tree shrew neurons. These findings provide new insights into the role of the miR_146-Tfdp2 axis in METH-induced neurotoxic injury and offer a theoretical basis for miR_146 as potential therapeutic targets in drug abuse.