Acupuncture is a potential strategy for the treatment of Alzheimer’s disease (AD) and the possible mechanisms worth to be explored. In this study, we proposed and tested the hypothesis that whether Notch signaling pathway is involved in the effect of electroacupuncture (EA) treatment. Rats that received EA treatment on the acupoints of Baihui (Du 20) and Shenshu (BL 23) had shorter latency and remained in the original platform quadrant longer and crossed the former platform contained quadrant more frequently compared to the Aβinjection rats without EA treatment. EA obviously alleviated the cell apoptosis resulted by Aβinfusion in hippocampus CA1 regions through upregulating the expression of Bcl-2 and downregulating the expression of Bax. EA could further obviously promote the expression of synapsin-1 and synaptophysin in hippocampus. Aβinjection significantly increased the expression of Notch1, Jag1, and Hes1 mRNA, while EA treatment downregulated the level of Notch1 and Hes1 mRNA in hippocampus, but not Jag1 mRNA. Our data suggested that EA treatment improved learning and memory function in the AD rat model partially through downregulating Notch signaling pathway.

Purpose. Our study is aimed at investigating the mechanism by which electroacupuncture (EA) promoted nerve regeneration by regulating the release of exosomes and exosome‐mediated miRNA‐21 (miR‐21) transmission. Furthermore, the effects of Schwann cells‐ (SC‐) derived exosomes on the overexpression of miR‐21 for the treatment of PNI were investigated. Methods. A sciatic nerve injury model of rat was constructed, and the expression of miR‐21 in serum exosomes and damaged local nerves was detected using RT‐qPCR after EA treatment. The exosomes were identified under a transmission electron microscope and using western blotting analysis. Then, the exosome release inhibitor, GW4869, and the miR‐21‐5p‐sponge used for the knockdown of miR‐21 were used to clarify the effects of exosomal miR‐21 on nerve regeneration promoted by EA. The nerve conduction velocity recovery rate, sciatic nerve function index, and wet weight ratio of gastrocnemius muscle were determined to evaluate sciatic nerve function recovery. SC proliferation and the level of neurotrophic factors were assessed using immunofluorescence staining, and the expression levels of SPRY2 and miR‐21 were detected using RT‐qPCR analysis. Subsequently, the transmission of exosomal miR‐21 from SC to the axon was verified in vitro. Finally, the exosomes derived from the SC infected with the miR‐21 overexpression lentivirus were collected and used to treat the rat SNI model to explore the therapeutic role of SC‐derived exosomes overexpressing miR‐21. Results. We found that EA inhibited the release of serum exosomal miR‐21 in a PNI model of rats during the early stage of PNI, while it promoted its release during later stages. EA enhanced the accumulation of miR‐21 in the injured nerve and effectively promoted the recovery of nerve function after PNI. The treatment effect of EA was attenuated when the release of circulating exosomes was inhibited or when miR‐21 was downregulated in local injury tissue via the miR‐21‐5p‐sponge. Normal exosomes secreted by SC exhibited the ability to promote the recovery of nerve function, while the overexpression of miR‐21 enhanced the effects of the exosomes. In addition, exosomal miR‐21 secreted by SC could promote neurite outgrowth in vitro. Conclusion. Our results demonstrated the mechanism of EA on PNI from the perspective of exosome‐mediated miR‐21 transport and provided a theoretical basis for the use of exosomal miR‐21 as a novel strategy for the treatment of PNI.

Growing evidence indicates that electroacupuncture (EA) has a definite effect on the treatment of peripheral nerve injury (PNI), but its mechanism is not completely clear. MicroRNAs (miRNAs) are involved in the regulation of a variety of biological processes, and EA may enhance PNI repair by regulating miRNAs. In this study, the rat sciatic nerve injury model was treated with EA for 4 weeks. Acupoints Huantiao (GB30) and Zusanli (ST36) were stimulated by EA 20 min once a day, 6 days a week for 4 weeks. We found that EA treatment downregulated the expression of miR-1b in the local injured nerve. In vitro experiments showed that overexpression of miR-1b inhibited the expression of brain-derived neurotrophic factor (BDNF) in rat Schwann cell (SC) line, while BDNF knockdown inhibited the proliferation, migration, and promoted apoptosis of SCs. Subsequently, the rat model of sciatic nerve injury was treated by EA treatment and injection of agomir-1b or antagomir-1b. The nerve conduction velocity ratio (NCV), sciatic functional index (SFI), and S100 immunofluorescence staining were examined and showed that compared with the model group, NCV, SFI, proliferation of SC, and expression of BDNF in the injured nerves of rats treated with EA or EA + anti-miR-1b were elevated, while EA + miR-1b was reduced, indicating that EA promoted sciatic nerve function recovery and SC proliferation through downregulating miR-1b. To summarize, EA may promote the proliferation, migration of SC, and nerve repair after PNI by regulating miR-1b, which targets BDNF.

Mood disorders mainly affect the patient’s daily life, lead to suffering and disability, increase the incidence rate of many medical illnesses, and even cause a trend of suicide. The glucocorticoid (GC)-mediated hypothalamus–pituitary–adrenal (HPA) negative feedback regulation plays a key role in neuropsychiatric disorders. The balance of the mineralocorticoid receptor (MR)/glucocorticoid receptor (GR) level contributes to maintaining the homeostasis of the neuroendocrine system. Consistently, a chronic excess of GC can also lead to HPA axis dysfunction, triggering anxiety, depression, memory loss, and cognitive impairment. The animal model induced by chronic corticosterone (CORT) administration has been widely adopted because of its simple replication and strong stability. This review summarizes the behavioral changes and underlying mechanisms of chronic CORT administration-induced animal models, including neuroinflammatory response, pyroptosis, oxidative stress, neuroplasticity, and apoptosis. Notably, CORT administration at different doses and cycles can destroy the balance of the MR/GR ratio to make dose-dependent effects of CORT on the central nervous system (CNS). This work aims to offer an overview of the topic and recommendations for future cognitive function research.