ABSTRACT
Epilepsy is a common neurological disorder in the central nervous system. Inflammation disrupts the blood-brain barrier (BBB), which is responsible for maintaining brain homeostasis. This study was aimed to investigate the functional role of microRNA (miR)-132 in hippocampal HT-22 cells under lipopolysaccharide (LPS) stimulation. In vitro cell inflammatory model was constructed by LPS stimulation. Inflammatory cell injury was evaluated according to the alterations of cell viability, apoptosis, and expression of inflammatory cytokines. Then, miR-132 level after LPS treatment was assessed. Subsequently, miR-132 was abnormally expressed after cell transfection, and the effects of miR-132 on LPS-induced cell inflammatory injury as well as phosphorylated levels of key kinases in the NF-κB and MAPK kinase (MEK)/ERK pathways were determined. The target gene of miR-132 was virtually screened and verified, and whether miR-132 affected HT-22 cells under LPS stimulation through regulating the target gene was verified. The results showed that the level of miR-132 was down-regulated by LPS in HT-22 cells, and the LPS-induced inflammatory injury could be reduced by miR-132 overexpression. Then, the phosphorylated levels of kinases in the NF-κB and MEK/ERK pathways were decreased by miR-132 overexpression. Tumor necrosis factor receptor-associated factor 6 (TRAF6) was predicted and verified to be a target of miR-132. Moreover, the alterations induced by miR-132 overexpression in the LPS-treated HT-22 cells were abrogated by TRAF6 overexpression. Therefore, we drew the conclusion that LPS down-regulated miR-132 and miR-132 attenuated LPS-induced inflammatory cell injury by targeting TRAF6, along with the inhibition of the NF-κB and MEK/ERK pathways.
Subject(s)
Inflammation/prevention & control , MicroRNAs/genetics , Neurons/drug effects , TNF Receptor-Associated Factor 6/metabolism , Animals , Apoptosis , Cell Survival , Cells, Cultured , Cytokines , Inflammation/chemically induced , Inflammation/genetics , Lipopolysaccharides/toxicity , MAP Kinase Signaling System/drug effects , Mice , NF-kappa B/genetics , NF-kappa B/metabolism , Neurons/immunology , Neurons/metabolism , Phosphorylation , Signal Transduction , TNF Receptor-Associated Factor 6/geneticsABSTRACT
Resveratrol is a natural polyphenol widely present in plants, particularly in the skin of red grapes and in wine. It possesses a wide range of biological effects and exhibits neuroprotective effects in numerous diseases. However, data evaluating the effects of resveratrol in vascular dementia (VaD) are lacking. In the present study, the permanent, bilateral common carotid artery occlusion rat model was used to study the effects of resveratrol on VaD. The Morris water maze was used to test the spatial learning and memory performance of the rats. The expression levels of Bax, Bcl-2, cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) in the hippocampus were measured. The results showed that resveratrol inhibited memory impairment in the VaD rat model, and attenuated the increases in the expression levels of Bax, cleaved caspase-3 and cleaved PARP and the reductions in the expression levels of Bcl-2 that were induced by VaD. These results provide a novel insight into the neuroprotective effects of resveratrol and its possible therapeutic role in VaD.
