NEFL Modulates NRN1-Mediated Mitochondrial Pathway to Promote Diacetylmorphine-Induced Neuronal Apoptosis.

Abstract

Diacetylmorphine abuse is a major social problem that jeopardizes the world, and abuse can cause serious neurological disorders. Apoptosis plays an important role in neurological diseases. A previous study by our group found that the brain tissue of diacetylmorphine-addicted rats showed severe vacuole-like degeneration and increased apoptosis, but the exact mechanism has not yet been reported. We used TMT technology to sequence the diseased brain tissue of rats, and selected neurofilament light chain (NEFL) and neuritin (NRN1) as the focus of our research. We explore the possible roles and mechanisms played by both. Based on the construction of apoptotic cell model, we used overexpression/silencing lentiviral vectors to interfere with the expression of NEFL in PC12 cells, and the results suggested that NEFL could regulate NRN1 to affect the apoptosis level. To further understand the specific mechanism, we used transmission electron microscopy to observe the ultrastructure of apoptotic cells, and the results showed that compared with the control group, mitochondria in the model group showed obvious vacuolation as well as expansion, a significant increase in the accumulation of ROS, and a significant decrease in the mitochondrial membrane potential; after overexpression/silencing of NEFL, these changes were found to occur along with the alteration of NEFL expression. In summary, we conclude that diacetylmorphine induces neuronal apoptosis, and the specific mechanism is that NEFL regulates the NRN1-mediated mitochondrial pathway to promote apoptosis.