Abstract
Chronic dysregulation of the intracellular Ca2+ homeostasis (excitotoxicity) is thought to contribute to the development of motor neuron diseases. Valproic acid (VPA) is widely used as an antiepileptic drug and acts mainly by inhibition of sodium channels and by enhancing the level of the inhibitory neurotransmitter γ-aminobutyric acid. Neuroprotective capacities of VPA are supposed to arise also from the inhibition of histone deacetylases. We investigated the viability of highly purified rat embryonic motor neurons cultured on glial feeder layers, composed of either astrocytes or Schwann cells, or in the absence of glia, monoculture in presence of VPA and/or kainate (KA) using immunocytochemistry and calcium imaging. A significant effect of the culture and co-culture conditions on the viability of motor neurons in our in vitro model of excitotoxicity was detected. The neuroprotective effect of VPA on primary embryonic motor neuron cultures was not proven. A functional interaction between VPA and KA occurred during the first 10 days in culture.
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Abbreviations
- VPA:
-
Valproic acid
- KA:
-
Kainate
- ALS:
-
Amyotrophic lateral sclerosis
- GABA:
-
γ-Aminobutyric acid
- AMPA:
-
α-Amino-3-hydroxy-5-methyl-4-isoxasole propionic acid
- HDAC:
-
Histone deacetylase
- GSK-3b:
-
Glycogen synthase kinase 3-b
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Acknowledgments
This work was supported by grants of the Deutsche Gesellschaft für Muskelkranke (DGM) to S. Petri and K. Krampfl and by Georg–Christoph–Lichtenberg scholarship of the state of Lower Saxony (DR). The authors wish to thank C. Hotopp-Herrgesell, M. Wesemann and A. Niesel for expert technical assistance.
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Ragancokova, D., Jahn, K., Kotsiari, A. et al. Analysis of Neuroprotective Effects of Valproic Acid on Primary Motor Neurons in Monoculture or Co-cultures with Astrocytes or Schwann Cells. Cell Mol Neurobiol 29, 1037–1043 (2009). https://doi.org/10.1007/s10571-009-9393-3
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DOI: https://doi.org/10.1007/s10571-009-9393-3