Effect and Mechanism of LIN28 on Ferroptosis in Mg2+-free Rat Hippocampal Neuron Model of Epilepsy.

Abstract

Studies have demonstrated that LIN28 is expressed in the CNS and may exert protective effects on neurons. However, it remains unknown whether LIN28 regulates ferroptosis in the context of epilepsy. In this study, we established an epilepsy model by culturing hippocampal neurons from rats in a magnesium-free (Mg2+-free) medium. In Mg2+-depleted conditions, hippocampal neurons exhibited reduced LIN28 expression, heightened miR-142-5p expression, decreased glutathione peroxidase (GPX) activity and expression, elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA), resulting in a significant decline in cell viability and an increase in ferroptosis. Conversely, overexpression of LIN28 reversed these trends in the mentioned indices. Altogether, this study reveals that LIN28 may exert neuroprotective effects by inhibiting the miR-142-5p expression and suppressing ferroptosis in hippocampal neurons induced by Mg2+-free via increasing GPX4 expression.