Long-term ethanol exposure impairs neuronal differentiation of human neuroblastoma cells involving neurotrophin-mediated intracellular signaling and in particular protein kinase C

Alcoholism, Clinical and Experimental Research
Julian HellmannCatrin Wernicke

Abstract

Revealing the molecular changes in chronic ethanol-impaired neuronal differentiation may be of great importance for understanding ethanol-related pathology in embryonic development but also in the adult brain. In this study, both acute and long-term effects of ethanol on neuronal differentiation of human neuroblastoma cells were investigated. We focused on several aspects of brain-derived neurotrophic factor (BDNF) signaling because BDNF activates the extracellular signal-regulated kinase (ERK) cascade, promoting neuronal differentiation including neurite outgrowth. The effects of ethanol exposure on morphological differentiation, cellular density, neuronal marker proteins, basal ERK activity, and ERK responsiveness to BDNF were measured over 2 to 4 weeks. qRT-PCR and Western blotting were performed to investigate the expression of neurotrophin receptor tyrosin kinase B (TrkB), members of the ERK-cascade, protein kinase C (PKC) isoforms and Raf-Kinase-Inhibitor-Protein (RKIP). Chronic ethanol interfered with the development of a neuronal network consisting of cell clusters and neuritic bundles. Furthermore, neuronal and synaptic markers were reduced, indicating impaired neuronal differentiation. BDNF-mediated activation of the ...Continue Reading

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Citations

May 13, 2011·European Archives of Psychiatry and Clinical Neuroscience·Julian HellmannGolo Kronenberg
Mar 22, 2012·European Archives of Psychiatry and Clinical Neuroscience·Julian Hellmann-RegenGolo Kronenberg
Jun 14, 2012·Cancer Metastasis Reviews·Gary G Meadows
Jun 17, 2011·Alcoholism, Clinical and Experimental Research·Tara A LindsleyElizabeth A Ruggiero
Jan 30, 2013·Journal of Cellular Physiology·Fahd Al-MullaKam C Yeung
Apr 6, 2011·Alcoholism, Clinical and Experimental Research·Roberta ZanardiniLuisella Bocchio-Chiavetto
Dec 28, 2018·Alcoholism, Clinical and Experimental Research·Polliana Toledo NunesLisa M Savage
May 30, 2017·Frontiers in Behavioral Neuroscience·Alessandra T PeanaElio Acquas
Jun 19, 2019·Oxidative Medicine and Cellular Longevity·Bong Seok KwonHo Jin Heo
Apr 11, 2020·Cell Chemical Biology·Hülya BayırValerian E Kagan

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