Granule cell migration influences the laminar structure of the cerebellum and thereby affects cerebellum function. Bergmann glia are derived from radial glial cells and aid in granule cell radial migration by providing a scaffold for migration and by mediating interactions between Bergmann glia and granule cells. In this review, we summarize Bergmann glia characteristics and the mechanisms underlying the effect of Bergmann glia on the radial migration of granule neurons in the cerebellum. Furthermore, we will focus our discussion on the important factors involved in glia-mediated radial migration so that we may elucidate the possible mechanistic pathways used by Bergmann glia to influence granule cell migration during cerebellum development.
Liver X receptors (LXRs) are nuclear receptors involved in the regulation of lipid metabolism and inflammatory responses in the central nervous system. Defects in cholesterol homeostasis contribute to the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and Huntington's disease. Inflammatory responses could enhance the neurodegenerative process or act independently. The natural and synthetic LXR agonists induce the transcriptional activity of LXR target genes, thus attenuate the imbalance of cholesterol metabolism and overactivation of microglia and astrocytes in inflammation and are widely used in a variety of neurodegenerative diseases animal models. By developing more specific, potent, penetrable, and functional LXR agonist may lead to a better curative effect for neurodegenerative diseases and avoidance of potentially deleterious side effects. Here, we focus on recent advances in our understanding of the role of LXRs and their agonists in cholesterol homeostasis, inflammation, and the potential therapeutic effects in neurodegenerative diseases.
Alzheimer's disease (AD) is the most prevalent type of dementia, and its neuropathology is characterized by deposition of insoluble β-amyloid peptides, intracellular neurofibrillary tangles, and the loss of diverse neurons. Current pharmacological treatments for AD relieve symptoms without affecting the major pathological characteristics of the disease. Therefore, it is essential to develop new and effective therapies. Stem-cell types include tissue-specific stem cells, such as neural stem cells and mesenchymal stem cells, embryonic stem cells derived from blastocysts, and induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells. Recent preclinical evidence suggests that stem cells can be used to treat or model AD. The mechanisms of stem cell based therapies for AD include stem cell mediated neuroprotection and trophic actions, antiamyloidogenesis, beneficial immune modulation, and the replacement of the lost neurons. iPSCs have been recently used to model AD, investigate sporadic and familial AD pathogenesis, and screen for anti-AD drugs. Although considerable progress has been achieved, a series of challenges must be overcome before stem cell based cell therapies are used clinically for AD patients. This review highlights the recent experimental and preclinical progress of stem-cell therapies for AD, and discusses the translational challenges of their clinical application.
High-sensitive cardiac troponin T (hs-TnT) is a critical biomarker in diagnosis of acute myocardial infarction (AMI). However, CKD individuals usually have elevated hs-TnT even in the absence of AMI.Our study aimed to explore the optimal cutoff-value of hs-TnT and further to improve diagnostic accuracy of AMI in CKD patients. Clinical data of 489 patients were collected from the maintained database between September 2010 and June 2014. CKD patients with AMI were assigned to CKD+AMI group and CKD patients without AMI were assigned to CKD group. Receiver operating characteristic curves were utilized to derive the optimal cutoff-value. In CKD+STEMI and CKD group, hs-TnT was increased with descending eGFR. In CKD+NSTEMI group, hs-TnT showed an upward trend with increasing SYNTAX Score. In patients with CKD+STEMI, hs-TnT was significantly correlated with SYNTAX Score in CKD stage 2, stage 4 and in total. In CKD patients, the optimal cutoff-value of hs-TnT for diagnosis of AMI was 129.45 ng/l with 75.2% sensitivity and 83.2% specificity. The cutoff-value appeared to be hs-TnT level of 99.55ng/l in CKD stage 3, 129.45 ng/l in CKD stage 4, 105.50 ng/l in CKD stage 5 and 149.35 ng/l in dialysis patients, respectively. In different stages of CKD, eGFR-range-specific optimal cutoff-values should be considered.Patients with CKD are at high risk of cardiovascular disease (CVD), have worse prognosis with higher mortality after AMI, and have higher risk of recurrent AMI, heart failure and sudden cardiac death 1 . Early diagnosis and intervention have been considered the cornerstone of improving prognosis of AMI in these individuals. Cardiac troponinT (cTnT), a critical biomarker in the diagnosis of AMI, is a low-molecular-weight protein that forms part of the troponin complex acting as an integral component in the myofibrillar contractile apparatus. Loss of integrity of cardiac myocyte membranes causes release of cardiac troponins into circulation, which can be detected by highly sensitive assays developed for cTnT to diagnose AMI 2 . However, elevation of serum cTnT concentration can occur in the absence of AMI, especially in CKD. Numerous data have proven that elevated hs-TnT levels are common in CKD patients 3-5 and in end stage renal disease (ESRD) patients this tendency has been observed in 20-90% of subjects 6 . With the progression of CKD, subjects with renal dysfunction have gradually elevated troponin levels 7 .KDIGO guidelines 1 recommend that in people with GFR < 60 ml/min/1.73 m 2 , serum troponin should be interpreted with caution in the diagnosis of acute coronary syndrome. Nevertheless, there is limited data on "expected" value of cTnT for diagnosis of AMI in CKD individuals. Current reference values of cardiac biomarkers to diagnose AMI were based on healthy individuals and were proven to have poor diagnostic accuracy among CKD patients 8,9 , which has brought great challenges for clinics. Recently, Twerenbold and colleagues reported optimal cutoff level of more sensitive cardiac troponin assay for diagnosis of...
Several psychiatric disorders are associated with aberrant white matter development, suggesting oligodendrocyte and myelin dysfunction in these diseases. There are indications that radial glial cells (RGCs) are involved in initiating myelination, and may contribute to the production of oligodendrocyte progenitor cells (OPCs) in the dorsal cortex. Liver X receptors (LXRs) are involved in maintaining normal myelin in the central nervous system (CNS), however, their function in oligodendrogenesis and myelination is not well understood. Here, we demonstrate that loss of LXRβ function leads to abnormality in locomotor activity and exploratory behavior, signs of anxiety and hypomyelination in the corpus callosum and optic nerve, providing in vivo evidence that LXRβ deletion delays both oligodendrocyte differentiation and maturation. Remarkably, along the germinal ventricular zone-subventricular zone and corpus callosum there is reduced OPC production from RGCs in LXRβ(-/-) mice. Conversely, in cultured RGC an LXR agonist led to increased differentiation into OPCs. Collectively, these results suggest that LXRβ, by driving RGCs to become OPCs in the dorsal cortex, is critical for white matter development and CNS myelination, and point to the involvement of LXRβ in psychiatric disorders.
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