ELK1 suppressed the progression of vascular dementia via modulating mTOR/CREB/YAP/TFEB signaling induced ferroptosis in hippocampal cells.

Abstract

To investigate the effects of ELK1 on hippocampal cells and its related mechanisms in the progression of vascular dementia (VD). Twenty-seven SD rats were divided into three groups: sham group (n = 9), Model group (n = 9), and Model+ELK1-OE group (n = 9). The VD animal model was established in the Model group by bilateral common carotid artery occlusion (BCCAO). The Morris water maze test was performed to observe the learning and memory abilities of the rats in the three groups. HE staining was used to examine the morphological changes in the hippocampal region, and immunohistochemical staining was conducted to observe the expression levels of ELK1. In the in vitro experiments, hippocampal tissues were isolated from rats in the sham group to prepare hippocampal single-cell suspensions. After different stimuli, Western blot was performed to observe protein expression, flow cytometry for apoptosis was used to assess hippocampal cell apoptosis, and a colorimetric assay kit was employed to detect the Fe2 + levels in the hippocampal cells of each group. In the in vivo experiments, the levels of ELK1 in VD rats were significantly lower than those in the sham group. ELK1 improved the learning and memory abilities of VD rats. After ELK1 intervention, the arrangement of neural cells in the hippocampal region of the rats was more regular, the nucleoli were clearer, the number of glial cells decreased, and the number of inflammatory cells was reduced. In the in vitro experiments, ELK1 promoted the expression of P-mTOR, P-CREB, and nuclear YAP, inhibited the expression of NOX4 and nuclear TFEB, and reduced hippocampal cell apoptosis and Fe2 + content. ELK1 inhibits the progression of vascular dementia by regulating mTOR/CREB/YAP/TFEB signaling-induced ferroptosis in hippocampal cells.