17/4/2014

Ascorbate prevents cell death from prolonged ... [J Neurosci Res. 2013] - PubMed - NCBI

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J Neurosci Res. 2013 Dec;91(12):1609-17. doi: 10.1002/jnr.23276. Epub 2013 Aug 30.

Ascorbate prevents cell death from prolonged exposure to glutamate in

an in vitro model of human dopaminergic neurons.
Ballaz S1, Morales I, Rodrguez M, Obeso JA.

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Abstract
Ascorbate (vitamin C) is a nonenzymatic antioxidant highly concentrated in the brain. In addition to
mediating redox balance, ascorbate is linked to glutamate neurotransmission in the striatum,
where it renders neuroprotection against excessive glutamate stimulation. Oxidative stress and
glutamatergic overactivity are key biochemical features accompanying the loss of dopaminergic
neurons in the substantia nigra that characterizes Parkinson's disease (PD). At present, it is not
clear whether antiglutamate agents and ascorbate might be neuroprotective agents for PD. Thus,
we tested whether ascorbate can prevent cell death from prolonged exposure to glutamate using
dopaminergic neurons of human origin. To this purpose, dopamine-like neurons were obtained by
differentiation of SH-SY5Y cells and then cultured for 4 days without antioxidant (antiaging)
protection to evaluate glutamate toxicity and ascorbate protection as a model system of potential
factors contributing to dopaminergic neuron death in PD. Glutamate dose dependently induced
toxicity in dopaminergic cells largely by the stimulation of AMPA and metabotropic receptors and
to a lesser extent by N-methyl-D-aspartate and kainate receptors. At relatively physiological levels
of extracellular concentration, ascorbate protected cells against glutamate excitotoxicity. This
neuroprotection apparently relies on the inhibition of oxidative stress, because ascorbate
prevented the pro-oxidant action of the scavenging molecule quercetin, which occurred over the
course of prolonged exposure, as is also seen with glutamate. Our findings show the relevance of
ascorbate as a neuroprotective agent and emphasize an often underappreciated role of oxidative
stress in glutamate excitotoxicity. Occurrence of a glutamate-ascorbate link in dopaminergic
neurons may explain previous contradictions regarding their putative role in PD.
Copyright 2013 Wiley Periodicals, Inc.
KEYWORDS: AMPA receptor, NMDA receptor, Parkinson's disease, SH-SY5Y, glutamate metabotropic
receptors, kainate receptor
PMID: 23996657 [PubMed - in process]

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