Schisandrin A and B affect the proliferation and differentiation of neural stem cells.

Schisandrin A and B (Sch A and B) are the important components of Asian dietary supplement and phytomedicine Schisandra chinensis (S. chinensis). They can enhance adult neurogenesis in vivo; however, these effects still need to be verified. Here NE-4 C neural stem cells (NSCs) were employed as the in vitro model and treated with Sch A and B at 0.1 µg/mL. EdU (5-Ethynyl-2'-deoxyuridine) labeling showed that both Sch A and B treatments enhanced NSC proliferation. Real-time PCR analysis showed the mRNA abundances of telomerase gene Tert and cell cycle gene Cyclin D1 were significantly up-regulated after the treatments. During the neurosphere induction, Sch B enhanced the neurosphere formation and neuronal differentiation, and increased the neurosphere semidiameters. Detection of the neuron differentiation marker Mapt indicates that both Sch A and B, especially Sch B, benefits the induced neuronal differentiation. Sch B treatment also enhanced mRNA expressions of the neurosphere-specific adhesion molecule Cdh2 and Wnt pathway-related genes including Mmp9, Cyclin D1 and ß-catenin. Together, Sch A especially Sch B, promotes the proliferation, affects the survival, differentiation and neurogenesis of NSCs, which is consistent with their in vivo effects. This study provides further clue on the potential neuropharmacological effects of S. chinensis.

Survivable potential of germ cells after trehalose cryopreservation of bovine testicular tissues.

Germplasm preservation of livestock or endangered animals and expansion of germline stem cells are important. The purpose of this study is to investigate whether supplementation of trehalose to the freezing medium (FM) reduces tissular damage and improves the quality of testicular cells in the cryopreserved bovine testicular tissues. We herein established an optimized protocol for the cryopreservation of bovine testicular tissues, and the isolation as well as culture of bovine germ cells containing spermatogonial stem cells (SSCs) from these tissues. The results showed that FM containing 10% dimethyl sulfoxide (Me2SO/DMSO), 10% knockout serum replacement (KSR) and 20% trehalose (FM5) combined with the uncontrolled slow freezing (USF) procedures has the optimized cryoprotective effect on bovine testicular tissues. The FM5 + USF protocol reduced the cell apoptosis, maintained high cell viability, supported the structural integrity and seminiferous epithelial cohesion similar to that in the fresh tissues. Viable germ cells containing SSCs were effectively isolated from these tissues and they maintained germline marker expressions in the co-testicular cells and co-mouse embryonic fibroblasts (MEF) feeder culture systems respectively, during the short-term culture. Additionally, upregulated transcriptions of spermatogenic differentiation marker C-KIT and meiotic marker SYCP3 were detected in these cells after retinoic acid-induced differentiation. Together, FM5 + USF is suitable for the cryopreservation of bovine testicular tissues, with benefits of reducing the apoptosis, maintaining the cell viability, supporting the testicular structure integrity, and sustaining the survival and differentiation potential of bovine germ cells containing SSCs.

GLP-1 receptor agonist liraglutide exerts central action to induce ß-cell proliferation through medulla to vagal pathway in mice.

Endogenous GLP-1 and GLP-1 receptor agonists (GLP-1RAs) regulate glucose metabolism via common and distinct mechanisms. Postprandial release of GLP-1 is modest and it is degraded by DPP-4 within 2 min, and hence it cannot enter the brain in substantial amount. In contrast, DPP-4-resistant GLP-1RAs are administered at 10 times higher concentration than endogenous GLP-1 level, which enables them to reach several brain regions including ARC and AP, the areas implicated in glucose metabolism. Hence, some of the effects of GLP-1RAs observed clinically and experimentally, including pancreatic ß-cell proliferation, are thought to involve the brain. However, the effects of centrally acting GLP-1/GLP-1RAs on glucose metabolism and underlying neural mechanism are unclear. This study aimed to establish the link of central GLP-1/GLP-1RA action to pancreatic ß-cell proliferation. Both subcutaneous (SC) and intracerebroventricular (ICV) injections of liraglutide increased the number of pancreatic ß-cells expressing Ki67 and PCNA, proliferation markers, in C57BL/6J mice. This effect was induced by single ICV administration of liraglutide at relatively low dose that was incapable of suppressing food intake. These SC and ICV liraglutide-induced effects were inhibited by 50% and 70%, respectively, by pretreatment with atropine, a muscarinic receptor blocker. ICV liraglutide induced c-Fos expression in the area postrema (AP), nucleus tractus solitaries (NTS), and dorsal motor nucleus of the vagus (DMX) of the brain stem. These results demonstrate that central action of liraglutide induces pancreatic ß-cell proliferation via the pathway involving the brain stem AP/NTS/DMX area and vagus nerve. This route is highly sensitive to GLP-1/GLP-1RA. Hence, this brain-pancreatic ß-cell pathway may operate in type 2 diabetic patients treated with GLP-RAs and serve to counteract the reduction of ß-cell mass.