Electroacupuncture stimulation attenuates corpus striatum white matter injury in rats with cerebral ischemia by inhibition of Nogo-A/NgR pathway / 针灸推拿医学（英文版）

Objective:To investigate the effect and the mechanism of electroacupuncture(EA)on corpus striatum white matter injury in rats with focal cerebral ischemia(FCI).Methods:Forty-four specific-pathogen-free Sprague-Dawley rats were divided into a normal group(n=10),a sham-operation group(sham group,n=10),and a modeling group(n=24)using the random number table method.The normal group was a blank control.In the sham group,only the vessels and vagus nerve were isolated without embolization.The FCI rat model in the modeling group was replicated using the middle cerebral artery occlusion embolization method.The 20 successfully modeled rats were randomly divided into a model group and an EA group,with 10 rats in each group.Rats in the model group did not receive further treatment.Rats in the EA group received EA stimulation at Baihui(GV20)and the left Zusanli(ST36)24 h after the successful modeling,30 min each time,once a day for 14 d.On the 14th day of the experiment,rats in each group were scored for neurological deficits and then sacrificed,and brain tissues containing corpus striatum around the ischemic focus were paraffin-embedded from 5 rats in each group.Luxol fast blue(LFB)staining was used to detect damage changes in the white matter.The positive immunoreactive expression of myelin basic protein(MBP),myelin-associated growth inhibitor A(Nogo-A)and its receptor(NgR)in rat corpus striatum tissue was detected by immunohistochemistry staining,and then the protein expression of MBP,Nogo-A,and NgR in the corpus striatum tissue around the ischemic focus was determined by Western blotting.Results:Compared with the normal group and the sham group,the model group had a significantly higher neurological deficit score(P＜0.05)and fiber bundle injuries in the corpus striatum white matter,evidenced by a significantly lower mean optical density value of corpus striatum LFB staining(P＜0.05),a significantly lower MBP expression level(P＜0.05),and significantly higher Nogo-A and NgR protein expression levels(P＜0.05).Compared with the model group,the neurological deficit score was significantly lower(P＜0.05),the mean optical density value of LFB staining was significantly higher(P＜0.05),the MBP expression level was increased(P＜0.05),and the expression levels of Nogo-A and NgR proteins were decreased(P＜0.05)in the EA group.Conclusion:EA reduces the ischemia-induced corpus striatum white matter injury and improves neurological deficits.The mechanism may be related to the inhibition of Nogo-A/NgR activation.

A Novel Role of Nogo Proteins: Regulating Macrophages in Inflammatory Disease.

Nogo proteins, also known as Reticulon-4, have been identified as myelin-derived inhibitors of neurite outgrowth in the central nervous system (CNS). There are three Nogo variants, Nogo-A, Nogo-B and Nogo-C. Recent studies have shown that Nogo-A/B is abundant in macrophages and may have a wider effect on inflammation. In this review, we focus mainly on the possible roles of Nogo-A/B on polarization and recruitment of macrophages and their involvement in a variety of inflammatory diseases. We then discuss the Nogo receptor1 (NgR1), a common receptor for Nogo proteins that is also abundant in microglia/macrophage in the CNS. Interaction of Nogo and NgR1 in microglia/macrophage may affect the adhesion and polarization of macrophages that are involved in multiple neurodegenerative diseases, including Alzheimer's disease and multiple sclerosis. Overall, this review provides insights into the roles of Nogo proteins in regulating macrophage functions and suggests that, potentially, Nogo proteins maybe a new target in the treatment of inflammatory diseases.

The Implication of Reticulons (RTNs) in Neurodegenerative Diseases: From Molecular Mechanisms to Potential Diagnostic and Therapeutic Approaches.

Reticulons (RTNs) are crucial regulatory factors in the central nervous system (CNS) as well as immune system and play pleiotropic functions. In CNS, RTNs are transmembrane proteins mediating neuroanatomical plasticity and functional recovery after central nervous system injury or diseases. Moreover, RTNs, particularly RTN4 and RTN3, are involved in neurodegeneration and neuroinflammation processes. The crucial role of RTNs in the development of several neurodegenerative diseases, including Alzheimer's disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), or other neurological conditions such as brain injury or spinal cord injury, has attracted scientific interest. Reticulons, particularly RTN-4A (Nogo-A), could provide both an understanding of early pathogenesis of neurodegenerative disorders and be potential therapeutic targets which may offer effective treatment or inhibit disease progression. This review focuses on the molecular mechanisms and functions of RTNs and their potential usefulness in clinical practice as a diagnostic tool or therapeutic strategy.

Association of genetic variations in RTN4 3'-UTR with risk for clear cell renal cell carcinoma.

Nogo proteins play an important role in the apoptosis of cells, especially in tumor cells. The present study was conducted to evaluate whether the TATC (rs71682980) and CAA (rs34917480) insertion/deletion polymorphisms of RTN4 3'-UTR are associated with clear cell renal cell carcinoma (ccRCC). These two polymorphisms were genotyped in 308 ccRCC patients and 466 healthy controls by polymerase chain reaction polyacrylamide gel electrophoresis (PCR-PAGE). Significantly reduced ccRCC risk was observed to be associated with the TATCins/ins genotype carriers (Versus TATCdel/del: adjusted OR 0.53, 95% CI 0.32-0.87, P = 0.022; Versus TATCdel/del-del/ins: adjusted OR 0.57, 95% CI 0.36-0.92, P = 0.017). After performing stratification analysis, the frequency of TATCins/ins genotype was observed to be significantly higher in patients with N0 compared the patients with N1 (P = 0.003). The present study provide evidence for the first time that the TATC insertion/deletion polymorphism in RTN4 3'-UTR may contributes to ccRCC risk in Chinese Han population.