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Neuroprotective effects of the beta‐catenin stabilization in an oxygen‐ and glucose‐deprived human neural progenitor cell culture system
Author(s) -
Skardelly Marco,
Gaber Khaled,
Schwarz Johannes,
Milosevic Javorina
Publication year - 2011
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2011.03.010
Subject(s) - neuroprotection , apoptosis , progenitor cell , wnt signaling pathway , neural stem cell , biology , programmed cell death , hypoxia (environmental) , necrosis , pharmacology , medicine , microbiology and biotechnology , chemistry , stem cell , signal transduction , biochemistry , oxygen , organic chemistry
β‐Catenin stabilization achieved either via GSK‐3β specific inhibition or involving canonical Wnt signalling pathway, contributes to neuroprotection in an oxygen–glucose deprivation (4 h OGD) in vitro hypoxia model performed on human cortical neural progenitor cells previously differentiated into neurons and glia. Neuroprotection mechanisms include both acquiring tolerance to injury throughout preconditioning (72 h prior to OGD) or being pro‐survival during 24 h reoxygenation after the insult. Four hours of OGD induced apoptotic cell death elevation to 73 ± 1% vs. 12% measured in control and the LDH level, indicative of necrotic cell injury, elevation by 67 ± 7% (set to 100%). A significant reduction in apoptosis occurred at 24 h reoxygenation with indirubin supplement which was 49 ± 6% at 2.5 μM BIO while LDH level was only 47 ± 5% of OGD. Kenpaullone was efficient in reducing both cell deaths at 5 μM (apoptosis 38 ± 1% and necrosis 33 ± 3% less than in OGD). Wnt agonist reduced apoptosis to 45 ± 3% at 0.01 μM, while LDH value was decreased to a level of 53 ± 5% of control. Our findings suggest that GSK‐3beta inhibitors/β‐catenin stabilizers may ultimately be useful drugs in neuroprotection and neuroregeneration therapies in vivo .