Valproic acid induces apoptosis in differentiating hippocampal neurons by the release of tumor necrosis factor-α from activated astrocytes

Neuroscience Letters
Caiying WangGuixiong Gu

Abstract

Human studies of neurodevelopment suggest that children exposed in utero to certain antiepileptic drugs (AEDs) suffer a variety of brain-behavior sequelae, such as neural tube defects, developmental delays, cognitive deficits, etc. Valproic acid (VPA), a commonly used AED, has greater risk for these side effects compared with other AEDs. However, the detailed molecular mechanisms underlying this developmental neurotoxicity of VPA is unclear despite previous research demonstrating that VPA could induce widespread apoptotic neurodegeneration in developing brains of animal models. This study characterizes the role of astrocytes in VPA-induced neurodegeneration. In developing brains, we evaluated the developmental neurotoxicity of VPA on differentiating neurons and astrocytes from neural progenitor cells cultured from the hippocampus of human fetuses. Exposure of a neuron-enriched culture to VPA at 250μM or 500μM did not cause neuronal apoptosis, but at 1mM and 7 days exposure, a slight increase in the percentage of apoptotic cells was observed. In contrast, VPA at 250μM to 1mM, selectively induced neuronal apoptosis in a neuron-astrocyte mixed cell culture model. The VPA-treated astrocytes showed morphological changes, and the lev...Continue Reading

References

Nov 6, 2002·Proceedings of the National Academy of Sciences of the United States of America·Petra BittigauChrysanthy Ikonomidou
Mar 18, 2004·Experimental Neurology·David C HessMakio Ogawa
Nov 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jenny HsiehFred H Gage
May 16, 2006·Experimental Neurology·Valérie BiranC Charriaut-Marlangue
Oct 20, 2006·Epilepsy & Behavior : E&B·Katriina ViinikainenReetta Kälviäinen
Jun 13, 2009·The European Journal of Neuroscience·David SchubertBarbara Blouw
Jun 18, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Silvia Alfonso-LoechesConsuelo Guerri

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Citations

Dec 5, 2013·Neuroscience and Biobehavioral Reviews·Fares Zeidán-ChuliáJosé Cláudio Fonseca Moreira
May 2, 2014·Brain & Development·Takeshi OhkawaraMasaaki Narita
Mar 13, 2016·Progress in Neurobiology·Glenn Dallérac, Nathalie Rouach
Mar 27, 2016·Archives of Toxicology·Marilena ColaiannaKarl-Heinz Krause
May 8, 2014·Reproductive Toxicology·A VerrottiG M Tiboni
Feb 1, 2015·Toxicology in Vitro : an International Journal Published in Association with BIBRA·William S CaoRobert F Halliwell
Aug 9, 2016·Journal of Biotechnology·Delyan P IvanovAnna M Grabowska
Jul 13, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Masahiro OkamotoTomoko Kuwabara
Jan 13, 2015·Journal of Neurochemistry·Dominique BollinoLaure Aurelian
Aug 31, 2018·Journal of Neuropathology and Experimental Neurology·Malgorzata Ziemka-NaleczTeresa Zalewska

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