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- Forsberg-Nilsson, Karin, et al.
(författare)
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Platelet-derived growth factor induces chemotaxis of neuroepithelial stem cells
- 1998
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Ingår i: Journal of Neuroscience Research. - 0360-4012 .- 1097-4547. ; 53:5, s. 521-530
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Tidskriftsartikel (refereegranskat)abstract
- The ability of differentiating cells to migrate within the developing central nervous system (CNS) depends on extrinsic guidance signals, some of which are growth factors. In this study we have investigated the chemotactic response of cultured stem cells from the embryonic rat cortex to platelet-derived growth factor (PDGF). Nestin-positive stem cells from the developing CNS can be maintained and expanded in vitro under serum-free conditions in the presence of basic fibroblast growth factor (bFGF). Northern blot analysis of PDGF receptor expression revealed both α- and β-receptors on bFGF-treated neural stem cells. Both PDGF-AA and PDGF-BB readily induced directed migration of cultured neuroepithelial cells as measured in a microchemotaxis assay. Blocking of the migratory response was achieved by incubation with PDGF isoform-specific antibodies. More than 90% of the migrating cells were nestin-positive and incorporation of BrdU was also seen suggesting the cells to be immature and not yet committed to a specific cell lineage. These findings suggest a role for PDGF in cell migration in the developing cortex.
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| 2. |
- Kullander, Klas, et al.
(författare)
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Specificity of neurotrophin-3 determined by loss-of-function mutagenesis
- 1997
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Ingår i: Journal of Neuroscience Research. - 0360-4012 .- 1097-4547. ; 50:3, s. 496-503
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Tidskriftsartikel (refereegranskat)abstract
- Neurotrophin-3 (NT-3) is a member of the family of neurotrophic factors, which also includes nerve growth factor (NGF) and which have specific activities on different subsets of vertebrate neurons. The aim of this study was to determine which residues in NT-3 direct its specificity to the cognate TrkC receptor. It was possible to replace 80% of the residues in NT-3 with NGF residues without loss of specific activity. Residues D72, Y85, R87, W101, S107, and A111, together with either the residues F12, V18, V20, M37, V42, F54, and K57 or the variable regions IV and V, accounted for the specificity of NT-3. It is concluded that NGF and NT-3 use overlapping as well as separated regions for determination of specificities for their cognate receptors TrkA and TrkC, respectively.
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| 4. |
- Parrow, V., et al.
(författare)
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Protein kinase C-alpha and -epsilon are enriched in growth cones of differentiating SH-SY5Y human neuroblastoma cells
- 1995
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Ingår i: Journal of Neuroscience Research. - : John Wiley & Sons. - 0360-4012 .- 1097-4547. ; 41:6, s. 782-791
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Tidskriftsartikel (refereegranskat)abstract
- SH-SY5Y cells differentiate into neuronal-like cells and express marker proteins like growth-associated protein (GAP-43) and neuropeptide tyrosine when treated with a low concentration (16 nM) of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) in the presence of growth factors or serum. Both control and differentiated cells expressed protein kinase C-alpha (PKC-alpha), PKC-epsilon, and PKC-zeta as revealed by Western blot analyses, but the subcellular distribution of the three isoforms was not uniform, indicating specific localized functions of the enzymes. In growth cones prepared from differentiating cells PKC-alpha and PKC-epsilon were enriched. In contrast, PKC-zeta was more evenly distributed within the differentiating cell. Cells treated with a high concentration of TPA (1.6 microM) differentiate poorly and continue to proliferate. In those cells, PKC-alpha and PKC-epsilon were found to be down-regulated while PKC-zeta remained present. Thus, down-regulation of PKC-alpha and PKC-epsilon appears to be incompatible with neuronal differentiation of SH-SY5Y cells. These cells also differentiate when treated with a combination of basic fibroblast growth factor and insulin-like growth factor I. Growth cones isolated from such cells are also enriched in PKC-alpha and PKC-epsilon, but not in PKC-zeta. Based on the subcellular distribution of PKC-alpha and epsilon, and that PKC substrates like GAP-43 and pp60c-src are enriched in SH-SY5Y growth cones, a role during neurite growth is suggested.
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| 7. |
- Beatus, P, et al.
(författare)
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Notch and neurogenesis
- 1998
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Ingår i: Journal of neuroscience research. - 0360-4012. ; 54:2, s. 125-136
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Tidskriftsartikel (refereegranskat)
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| 15. |
- Edström, A., et al.
(författare)
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Phospholipase A2 activity is required for regeneration of sensory axons in cultured adult sciatic nerves
- 1996
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Ingår i: Journal of Neuroscience Research. - 0360-4012. ; 43:2, s. 183-189
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Tidskriftsartikel (refereegranskat)abstract
- The adult frog dorsal root ganglia (DRGs) and their sciatic nerves (ScN) survive in organ culture for several days. About 3 days after a local test crush, the sensory axons start to regenerate into the distal nerve stump at a rate of approximately 0.6-0.9 mm/day. The axonal outgrowth is inhibited in a non-toxic way by low concentrations of three different phospholipase A2 (PLA2) inhibitors: 4-bromophenacyl bromide (BPB), aristolochic acid, and oleyl-oxyethyl-phosphoryl-choline (OOPC). In contrast, the outgrowth was slightly stimulated by 0.2 μM melittin, a PLA2 activator. Most experiments refer to the effects of BPB, which was shown to almost completely inhibit outgrowth at a concentration which did not affect either ganglionic protein synthesis or axonal transport. Using a compartmental system it could clearly be shown that BPB exerted its action in the outgrowth region. Other experiments showed that the initial period (about 3 days), which precedes the outgrowth, was unaffected by BPB. Several structures, including axonal ones, showed immunoreactivity for the low molecular form of PLA2 (sPLA2). The results suggest that PLA2 activity plays an important role in nerve regeneration and exerts its action at a local level, where the growth cones move forward.
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| 16. |
- Ekström, Per
(författare)
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Increased cyclic AMP in in vitro regenerating frog sciatic nerves inhibits Schwann cell proliferation bur has no effect on axonal outgrowth
- 1995
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Ingår i: Journal of Neuroscience Research. - : Wiley. - 0360-4012. ; 42:1, s. 54-62
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Tidskriftsartikel (refereegranskat)abstract
- In the present study the role of cAMP for axonal outgrowth and Schwann cell proliferation was studying using the cultured frog sciatic nerve. An intrinsic rise in nerve injury, both in vitro and in vivo. Treatment with 0.1‐1.0μM forskolin, an activator of the cAMP‐generating enzyme adenylyl cyclase, increased the cAMP content up to 13‐fold, but was yet without effect on axonal outgrowth during an 8‐day culturing period. HA‐1004, an inhibitor of cAMP‐dependent protein kinase, also lacked effect on the regeneraton. In contrast, the proliferation of Schwann cells, measured as [3H]thymidine incorporation, was inhibited to about 70% of control by forskolin, whereas HA‐1004 stimulated proliferation to approximately 130% of control. The results suggest that cAMP is involved in the injury‐induced proliferation of Schwann cells of an adult peripheral nerve but that it lacks a central role in the regeneration of sensory axons of such nerves. © 1995 Wiley‐Liss, Inc.
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