miR-134-5p/Foxp2/Syn1 is involved in cognitive impairment in an early vascular dementia rat model

Forkhead box P2 (Foxp2) is a transcription factor involved in vocal learning. However, the number of previous studies that have investigated the role of Foxp2 in early vascular dementia (VD) is limited. The aim of the present study was to determine whether microRNA (miR)-134-5p/Foxp2 contributes to cognitive impairment in a chronic ischemia-induced early VD model. miR-134-5p was found to be significantly increased in the cortex in a rat VD model. Intracerebroventricular injection of miR-134-5p antagomir into VD rats prevented the loss of synaptic proteins and the development of cognitive impairment phenotypes. Histopathological analysis revealed that miR-134-5p aggravated cognitive impairment in VD rats through damage to cortical neurons and loss of synaptic proteins. Bioinformatics analysis predicted that miR-134-5p targets Foxp2 mRNA. Dual luciferase analysis and western blotting supported the prediction that miR-134-5p targets Foxp2. Furthermore, the silencing of Foxp2 significantly inhibited the effect of miR-134-5p on synaptic protein loss. Chromatin immunoprecipitation-quantitative polymerase chain reaction analysis indicated that Foxp2 binds to the synapsin I (Syn1) promoter at -400/-600 bp upstream of the transcription start site. In conclusion, the miR-134-5p/Foxp2/Syn1 axis was found to contribute to cognitive impairment in a chronic ischemia-induced early VD model, which may enable the development of new therapeutic strategies for the prevention and treatment of VD.