Low extracellular calcium is sufficient for survival and proliferation of murine mesencephalic neural precursor cells

Milošević, Javorina; Juch, Franziska; Storch, Alexander; Schwarz, Johannes

doi:10.1007/s00441-005-0147-3

Cited by 8 publications

(3 citation statements)

References 27 publications

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“…To test the former option, we studied the effects of insulin and IGF-I on the levels of PCNA (a cofactor of DNA polymerase-␦), which correlates with cell cycle (12,31). Immunohistochemical results (Fig.…”

Section: Effects Of Igf-i and Insulin On The Development Of MCmentioning

confidence: 99%

GLUT4 in murine bone growth: from uptake and translocation to proliferation and differentiation

Maor

Vasiliver-Shamis

Hazan-Brill

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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Skeletal growth, taking place in the cartilaginous growth plates of long bones, consumes high levels of glucose for both metabolic and anabolic purposes. We previously showed that Glut4 is present in growing bone and is decreased in diabetes. In the present study, we examined the hypothesis that in bone, GLUT4 gene expression and function are regulated via the IGF-I receptor (IGF-IR) and that Glut4 plays an important role in bone growth. Insulin and IGF-I actions on skeletal growth and glucose uptake were determined using mandibular condyle (MC) organ cultures and MC-derived primary cell cultures (MCDC). Chondrogenesis was determined by following proliferation and differentiation activities using immunohistochemical (IHC) analysis of proliferating cell nuclear antigen and type II collagen expression, respectively. Overall condylar growth was assessed morphometrically. GLUT4 mRNA and protein levels were determined using in situ hybridization and IHC, respectively. Glut4 translocation to the cell membrane was assessed using confocal microscopy analysis of GFP-Glut4 fusion-transfected cells and immunogold and electron microscopy on MC sections; glucose uptake was assayed by 2-deoxyglucose (2-DOG) uptake. Both IGF-I and insulin-stimulated glucose uptake in MCDC, with IGF-I being tenfold more potent than insulin. Blockage of IGF-IR abrogated both IGF-I- and insulin-induced chondrogenesis and glucose metabolism. IGF-I, but not insulin, induced Glut4 translocation to the plasma membrane. Additionally, insulin induced both GLUT4 and IGF-IR gene expression and improved condylar growth in insulin receptor knockout mice-derived MC. Moreover, silencing of GLUT4 gene in MCDC culture abolished both IGF-I-induced glucose uptake and chondrocytic proliferation and differentiation. In growing bone, the IGF-IR pathway stimulates Glut4 translocation and enhances glucose uptake. Moreover, intact Glut4 cellular levels and translocation machinery are essential for early skeletal growth.

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Section: Effects Of Igf-i and Insulin On The Development Of MCmentioning

confidence: 99%

GLUT4 in murine bone growth: from uptake and translocation to proliferation and differentiation

Maor

Vasiliver-Shamis

Hazan-Brill

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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“…Since oral calcium and/or vitamin D supplements may positively affect anxiety response and memory, they were further postulated to modulate the expression of doublecortin (DCX)-a neural system-specific microtubule-associated protein commonly used as an indirect biomarker of hippocampal neurogenesis and neuronal migration. The direct evidence that confirms the positive effects of extracellular calcium on neurogenesis is scant, but there are several purports suggesting that neurogenesis requires optimal levels of both extracellular and intracellular calcium [24,27].…”

Section: Introductionmentioning

confidence: 99%

Oral calcium and vitamin D supplements differentially alter exploratory, anxiety-like behaviors and memory in male rats

Lapmanee,

Bhubhanil,

Sriwong

et al. 2023

PLoS ONE

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Oral calcium and calcium plus vitamin D supplements are commonly prescribed to several groups of patients, e.g., osteoporosis, fracture, and calcium deficiency. Adequate and steady extracellular calcium levels are essential for neuronal activity, whereas certain forms of calcium supplement (e.g., CaCO3) probably interfere with memory function. However, it was unclear whether a long-term use of ionized calcium (calcium chloride in drinking water ad libitum), vitamin D supplement (oral gavage) or the combination of both affected anxiety and memory, the latter of which was probably dependent on the hippocampal neurogenesis. Here, we aimed to determine the effects of calcium and/or vitamin D supplement on the anxiety- and memory-related behaviors and the expression of doublecortin (DCX), an indirect proxy indicator of hippocampal neurogenesis. Eight-week-old male Wistar rats were divided into 4 groups, i.e., control, calcium chloride-, 400 UI/kg vitamin D3-, and calcium chloride plus vitamin D-treated groups. After 4 weeks of treatment, anxiety-, exploration- and recognition memory-related behaviors were evaluated by elevated pulse-maze (EPM), open field test (OFT), and novel object recognition (NOR), respectively. The hippocampi were investigated for the expression of DCX protein by Western blot analysis. We found that oral calcium supplement increased exploratory behavior as evaluated by OFT and the recognition index in NOR test without any effect on anxiety behavior in EPM. On the other hand, vitamin D supplement was found to reduce anxiety-like behaviors. Significant upregulation of DCX protein expression was observed in the hippocampus of both calcium- and vitamin D-treated rats, suggesting their positive effects on neurogenesis. In conclusion, oral calcium and vitamin D supplements positively affected exploratory, anxiety-like behaviors and/or memory in male rats. Thus, they potentially benefit on mood and memory in osteoporotic patients beyond bone metabolism.

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“…Hence, neuroscientists are focusing on new restorative approaches with human embryonic stem cells (hESCs) and fetal cell‐based treatments (http://www.gforce-pd.com and http://www.transeuro.org.uk) . Along with hESCs , , and genetically modified induced pluripotent stem cells (IPSCs) , , , human midbrain‐derived neural progenitor cells (hmNPCs) have the capacity to self‐renew and to differentiate into dopaminergic (DA) neurons . Here, we report that hmNPCs remain fate specific and differentiate into defined, authentic A9‐specific dopaminergic neurons.…”

Section: Introductionmentioning

confidence: 99%

Preclinical Analysis of Fetal Human Mesencephalic Neural Progenitor Cell Lines: Characterization and Safety In Vitro and In Vivo

Moon

Schwarz

Lee

et al. 2016

Stem Cells Translational Medicine

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We have developed a good manufacturing practice for long‐term cultivation of fetal human midbrain‐derived neural progenitor cells. The generation of human dopaminergic neurons may serve as a tool of either restorative cell therapies or cellular models, particularly as a reference for phenotyping region‐specific human neural stem cell lines such as human embryonic stem cells and human inducible pluripotent stem cells. We cultivated 3 different midbrain neural progenitor lines at 10, 12, and 14 weeks of gestation for more than a year and characterized them in great detail, as well as in comparison with Lund mesencephalic cells. The whole cultivation process of tissue preparation, cultivation, and cryopreservation was developed using strict serum‐free conditions and standardized operating protocols under clean‐room conditions. Long‐term‐cultivated midbrain‐derived neural progenitor cells retained stemness, midbrain fate specificity, and floorplate markers. The potential to differentiate into authentic A9‐specific dopaminergic neurons was markedly elevated after prolonged expansion, resulting in large quantities of functional dopaminergic neurons without genetic modification. In restorative cell therapeutic approaches, midbrain‐derived neural progenitor cells reversed impaired motor function in rodents, survived well, and did not exhibit tumor formation in immunodeficient nude mice in the short or long term (8 and 30 weeks, respectively). We conclude that midbrain‐derived neural progenitor cells are a promising source for human dopaminergic neurons and suitable for long‐term expansion under good manufacturing practice, thus opening the avenue for restorative clinical applications or robust cellular models such as high‐content or high‐throughput screening. Stem Cells Translational Medicine 2017;6:576–588

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Low extracellular calcium is sufficient for survival and proliferation of murine mesencephalic neural precursor cells

Cited by 8 publications

References 27 publications

GLUT4 in murine bone growth: from uptake and translocation to proliferation and differentiation

GLUT4 in murine bone growth: from uptake and translocation to proliferation and differentiation

Oral calcium and vitamin D supplements differentially alter exploratory, anxiety-like behaviors and memory in male rats

Preclinical Analysis of Fetal Human Mesencephalic Neural Progenitor Cell Lines: Characterization and Safety In Vitro and In Vivo

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