scholarly journals The Tripotential Glial-Restricted Precursor (GRP) Cell and Glial Development in the Spinal Cord: Generation of Bipotential Oligodendrocyte-Type-2 Astrocyte Progenitor Cells and Dorsal–Ventral Differences in GRP Cell Function

2002 ◽  
Vol 22 (1) ◽  
pp. 248-256 ◽  
Author(s):  
Ninel Gregori ◽  
Christoph Pröschel ◽  
Mark Noble ◽  
Margot Mayer-Pröschel
1989 ◽  
Vol 109 (5) ◽  
pp. 2405-2416 ◽  
Author(s):  
C Godfraind ◽  
V L Friedrich ◽  
K V Holmes ◽  
M Dubois-Dalcq

C57 BL/6N mice injected intracranially with the A59 strain of mouse hepatitis virus exhibit extensive viral replication in glial cells of the spinal cord and develop demyelinating lesions followed by virus clearing and remyelination. To study how different glial cell types are affected by the disease process, we combine three-color immunofluorescence labeling with tritiated thymidine autoradiography on 1-micron frozen sections of spinal cord. We use three different glial cell specific antibodies (a) to 2',3' cyclic-nucleotide 3' phosphohydrolase (CNP) expressed by oligodendrocytes, (b) to glial fibrillary acidic protein (GFAP) expressed by astrocytes, and (c) the O4 antibody which binds to O-2A progenitor cells in the rat. These progenitor cells, which give rise to oligodendrocytes and type 2 astrocytes and react with the O4 antibody in the adult central nervous system, were present but rare in the spinal cord of uninfected mice. In contrast, cells with the O-2A progenitor phenotype (O4 + only) were increased in number at one week post viral inoculation (1 WPI) and were the only immunostained cells labeled at that time by a 2-h in vivo pulse of tritiated thymidine. Both GFAP+ only and GFAP+, O4+ astrocytes were also increased in the spinal cord at 1 WPI. Between two and four WPI, the infected spinal cord was characterized by the loss of (CNP+, O4+) oligodendrocytes within demyelinating lesions and the presence of O-2A progenitor cells and O4+, GFAP+ astrocytes, both of which could be labeled with thymidine. As remyelination proceeded, CNP immunostaining returned to near normal and tritiated thymidine injected previously during the demyelinating phase now appeared in CNP+ oligodendrocytes. Thus O4 positive O-2A progenitor cells proliferate early in the course of the demyelinating disease, while CNP positive oligodendrocytes do not. The timing of events suggests that the O-2A progenitors may give rise to new oligodendrocytes and to type 2 astrocytes, both of which are likely to be instrumental in the remyelination process.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A319-A319
Author(s):  
Seshagiri R Nandula ◽  
Rajesh Janapala ◽  
Sabyasachi Sen

Abstract Introduction: Peripheral blood derived CD34 +ve Endothelial progenitor cells (EPCs) has been shown to help vascular regeneration and are dysfunctional in subjects with type 2 diabetes mellitus (T2DM) leading to poor endothelial cell function (ECF). We conducted two separate clinical trials using Canagliflozin, an SGLT2 inhibitor and Linagliptin, a DPP4 inhibitor where these medications or matched placebo was added to other oral antidiabetic medication such Metformin and Insulin. Our goal was to do a comparative analysis based on the effect of the medications on CD34+ve hematopoetic progenitor cell function such as migration, colony formation and podocyte specific urine exosome analysis. Methods: Approximately 30 subjects were enrolled in the two studies 29 subjects were enrolled in this 12–16 weeks, double-blind, two-arm, randomized placebo matched trial, with 100 mg Canagliflozin (Cana, low dose) compared to placebo AND Linagliptin (Lina 5mg), compared to placebo. T2DM (30–70 years old), HbA1c of 7–10%, were included. Peripheral blood derived CD34+ cell number, migratory function, mRNA gene expression along with cardiometabolic parameters such as arterial stiffness, biochemistry, resting energy expenditure, and body composition were measured. Data were collected at weeks 0 (baseline), 6 or 8 (mid-point), and 12 or 16 (final). A mixed model regression analysis was done with a p-value <0.05 considered significant. Results: We found a statistically significant reduction in systolic (p=0.008) and diastolic (p=0.038) blood pressure in cana group. There was a statistically significant increase in adiponectin (p=0.0062) and trend level reduction in IL6 (p=0.16), indicating an anti-inflammatory effect of canagliflozin on endothelium, not seen in Lina group. There was an increase in mRNA expression of genes associated with endothelial function in CD34+ cells such as VEGFA, PECAM-1, a mature endothelial marker and NOS3 (or eNOS) with both Cana and Lina. There was improvement in CD34+ numbers by direct counting (not statistically significant) with both medications. Data on urine podocyte specific exosomal protein indicates an advantage with Cana compared to Lina, though it did not reach stat significance. Conclusions: Our study indicates that Canagliflozin improves several components of vascular function by improving adiponectin, reducing inflammatory cytokines, and by increasing expression of endothelium specific genes in CD34+ progenitor cells compared to Linagliptin.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yi Cui ◽  
Yanyun Yin ◽  
Zhifeng Xiao ◽  
Yannan Zhao ◽  
Bing Chen ◽  
...  

Abstract Background Emerging evidence suggests that miR-124 performs important biological functions in neural stem cells (NSCs); it regulates NSC behavior and promotes the differentiation of NSCs into neurons, but the exact molecular mechanism remains unknown. And also, the role of miR-124 during spinal cord injury regeneration is unclear. Materials and methods In order to explore the function of miR-124 in neural differentiation, the molecular markers (Tuj1, Map2, and GFAP) correlated with the differentiation of NSCs were detected by immunofluorescence staining both in cultured mouse spinal cord progenitor cells (SC-NPCs) and in spinal cord injury (SCI) animal models. The migration ability and apoptosis of cultured SC-NPCs were also evaluated by Transwell migration assay and TUNEL assay. In addition, the relative expression of lnRNA Neat1- and Wnt/β-catenin signaling-related genes were detected by quantitative real-time PCR. Results In this study, we revealed that lncRNA Neat1 is involved in regulating Wnt/β-catenin signaling that is activated by miR-124 in SC-NPCs. LncRNA Neat1 was also found to play an important role in regulating neuronal differentiation, apoptosis, and migration of SC-NPCs. Furthermore, we demonstrated that overexpression of miR-124 resulted in elevated Neat1 expression, accompanied with the functional recovery of locomotion in a mouse model of spinal cord injury. Conclusions Our results confirm the therapeutic effectiveness of miR-124 on the functional recovery of injured spinal cord, supporting the rationale and feasibility of miR-124 for spinal cord injury treatment in future clinical therapy. Furthermore, we concluded that the miR-124-Neat1-Wnt/β-catenin signaling axis is involved in regulating the cell function of SC-NPCs, and this may offer novel therapeutic avenues for future treatment of SCI.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1561-P
Author(s):  
SUZANNE CRAFT ◽  
AMY CLAXTON ◽  
MARK TRIPPUTI ◽  
SHARON EDELSTEIN ◽  
SILVA A. ARSLANIAN ◽  
...  

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1780-P
Author(s):  
KRISTINA UTZSCHNEIDER ◽  
LAURE EL GHORMLI ◽  
SUSAN SAM ◽  
DAVID A. EHRMANN ◽  
KIEREN J. MATHER ◽  
...  

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 970-P
Author(s):  
KRISHNAMOORTHY SATHEESH ◽  
CHAMUKUTTAN SNEHALATHA ◽  
ARUN NANDITHA ◽  
ARUN RAGHAVAN ◽  
RAMACHANDRAN VINITHA ◽  
...  

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 78-OR
Author(s):  
FARHAT FATIMA ◽  
JØRAN HJELMESÆTH ◽  
KARE I. BIRKELAND ◽  
HANNE L. GULSETH ◽  
JENS K. HERTEL ◽  
...  

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