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Einfluss von Valproat auf die neuronale/dopaminerge und gliale Differenzierung von neuronalen Vorläuferzellen / vorgelegt von: Kowalski, Michael

Valproat, Zelldetermination, Neuronale Differenzierung, Gliale Differenzierung, Stem cells, Valproicacid

PPN (Catalogue-ID): 848055756
Personen: Kowalski, Michael [VerfasserIn]
Cooperations/Conferences: Ernst-Moritz-Arndt-Universität Greifswald [Grad-verleihende Institution]
Format: eBook eBook
Language: German
Published: Greifswald, 2016
Hochschule: Dissertation, Universitätsmedizin der Ernst-Moritz-Arndt-Universität Greifswald, 2016
Basisklassifikation: 44.90
42.15
Subjects:

Valproinsäure / Zelldetermination / Gliazelle / Stammzelle

Formangabe: Hochschulschrift
Notes: Literaturverzeichnis: Seite 58-72.
Physical Description: 1 Online-Ressource (PDF-Datei: 83 Seiten, 1209 Kilobyte), Illustrationen (farbig), Diagramme (farbig).

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520 |a Valproat, Zelldetermination, Neuronale Differenzierung, Gliale Differenzierung, Stem cells, Valproicacid 
520 |a Background: VPA is a known inhibitor of PI3-kinase/Akt pathway. Inhibitory effects on GSK-3 (downstream effector of PI3-kinase), as well as direct effects on PI3-kinase are reported. Own previous studies showed that wortmannin (PI3-kinase inhibitor) and SN50 (NFkB-inhibitor) blocked astroglial differentiation of mesencephalic neural stem cells (NSCs). Neural differentiation promoting effects of VPA are as well discussed as effects inhibiting astroglial differentiation. Here we examined the effect of VPA on astroglial, oligodendroglial and neuronal differentiation. Toxic effects of VPA in used dosages were excluded in previous studies. Methods: NSCs were maintained in DMEM/F-12 (2:1) with 2% B27, 2% penicillin/streptomycin, 20 ng/ml EGF (37°C, humidified atmosphere, 5% CO2, 92% N2, 3±2% O2. NSCs were differentiated on poly-L-lysine in P4-8F without or with up to 300 ìg/ml VPA for up to 10 days. ELISA was carried out using FACE® kit. Immunocytochemistry was carried out using standard protocols. Antibodies: mouse anti-GalC monoclonal 1:300, rabbit anti-GFAP protein 1:750, mouse anti Tuj 1:500 (all Chemicon), mouse anti-MAP2 1:300 (BD Bioscience) and fluorescence labeled secondary antibodies (Invitrogen). Results: After differentiation in the presence of 300 ìg/ml VPA the number of GFAP+ cells was reduced to 56.6±3.0% (65.7±1.4% without VPA, p=0.02). For the number of GalC+ cells (11.8±2.30%/12.3±3.8; VPA/no VPA) we found no difference. For the number of Map2+ cells there was ... 
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