miR-124 Ameliorates Spatial Memory Deficits in Rats Exposed to Single-Prolonged Stress by Downregulating IQGAP1 to...

Post-traumatic stress disorder (PTSD) is a highly prevalent, trauma-induced psychiatric condition characterized by persistent cognitive-affective dysfunction. However, the pathogenesis of PTSD is not yet well understood. MicroRNA-124-3p (miR-124) plays an important role in neuroprotective function in various neurological disorders, and our previous study confirmed that hippocampal miR-124 expression is decreased in rats subjected to single-prolonged stress (SPS). In the present study, we found that miR-124 ameliorates spatial memory deficits in SPS rats. IQGAP1, which can promote neuronal structural remodeling to form functional neural networks, was upregulated in the hippocampus of SPS rats and was identified as a downstream target of miR-124, as confirmed by luciferase reporter assays. Furthermore, we demonstrated that miR-124 not only upregulated the expression of actin-binding proteins (ABPs), including drebrin1 and phosphorylated cofilin (p-cofilin), but also significantly reduced hippocampal neuronal apoptosis in SPS-exposed rats. Notably, IQGAP1 inhibition elevates drebrin1 expression and reduces neuronal apoptosis. Collectively, these findings demonstrate that miR-124 participates in the pathophysiological progression of PTSD by regulating ABP expression and neuronal apoptosis via targeting IQGAP1.