Long non-coding RNA MEG3 alleviates postoperative cognitive dysfunction by suppressing inflammatory response and oxidative stress via has-miR-106a-5p/SIRT3.

Postoperative cognitive dysfunction (POCD), a neurological complication after surgery, is common among the elderly in particular. Maternal expression gene 3 (MEG3) is a novel long non-coding RNA (lncRNA) that contributes to glial cell activation and inflammation. We aim to further explore its role in POCD. Mice were induced with sevoflurane anesthesia and underwent orthopedic surgery to establish a POCD model. BV-2 microglia activation was induced by lipopolysaccharide. The overexpressed lentiviral plasmid lv-MEG3 and its control were injected into mice. pcDNA3.1-MEG3, has-miR-106a-5p mimic, and its negative control were transfected into BV-2 cells. The expressions of has-miR-106a-5p MEG3 and Sirtuin 3 (SIRT3) in rat hippocampus and BV-2 cells were quantitatively detected. Levels of SIRT3, TNF-α, and IL-1ß were detected by western blot, levels of TNF-α and IL-1ß by ELISA, and expression of GSH-Px, SOD, and MDA by kits. The targeting relationship between MEG3 and has-miR-106a-5p was confirmed using bioinformatics and dual-luciferase reporter assay. LncRNA MEG3 was down-regulated in POCD mice, whereas has-miR-106a-5 levels were up-regulated. Overexpression of MEG3 could attenuate cognitive dysfunction and inflammatory response in POCD mice, inhibit lipopolysaccharide-induced inflammatory response and oxidative stress in BV-2 cells, and promote has-miR-106a through competitive binding with has-miR-106a-5-5 expression of target gene SIRT3. Overexpression of has-miR-106a-5p had a reverse effect on overexpression of MEG3 functioning on lipopolysaccharide-induced BV-2 cells. LncRNA MEG3 could inhibit the inflammatory response and oxidative stress via has-miR-106a-5p/SIRT3, thereby reducing POCD, which might be a potential biological target for the diagnosis and treatment of clinical POCD.

Effect of neurotropin on Alzheimer's disease-like changes and cognitive function in rats with chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion (CCH) is a main mechanism of cerebrovascular disease and is associated with various cerebrovascular and neurodegenerative diseases, including Alzheimer's disease. However, treatment of CCH in clinical practice is not ideal, but neurotropin (NTP) has been shown to have a neuroprotective effect. Therefore, this study examined the effect and possible mechanism of NTP in nerve injury caused by CCH. A rat CCH model was established by bilateral common carotid artery occlusion (2VO), and rats were treated with intragastric administration of NTP (200 nu/kg/day) for 28 consecutive days. After treatment, rats were subjected to the Morris water maze and novel object recognition test. Subsequently, an ELISA was applied to detect amyloid-ß (Aß) 1-40 and Aß1-42 levels in rat hippocampal tissues, quantitative reverse transcription PCR assays were used to detect the mRNA expression levels of brain-derived neurotrophic factor (BDNF) and Trk B, and Western blots were used to detect the protein expression levels of BACE1, tau, p-tau, and protein kinase B (Akt)/glycogen synthase kinase 3ß (GSK3ß) pathway-related proteins. The rat model of CCH was successfully established by 2VO. Behavioral tests indicated that the cognitive ability of 2VO rats was severely impaired. NTP treatment greatly ameliorated the cognitive disability, reduced Aß1-40 and Aß1-42 levels and tau phosphorylation, and upregulated BACE1, Trk B, and BDNF expression in the hippocampus of 2VO rats. Finally, we found that NTP markedly activated Akt/GSK3ß pathway activity. NTP can ameliorate cognitive disability in CCH rats possibly by reducing Aß accumulation and tau phosphorylation in the hippocampus. These effects of NTP may be related to the Akt/GSK3ß pathway activation. NTP may be a promising new drug candidate for CCH patients.