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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 inan in vitro model of human dopaminergic neurons.

Ballaz S , Morales I, Rodríguez M, Obeso JA.

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 andglutamatergic 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.

 AMPA receptor, NMDA receptor, Parkinson's disease, SH-SY5Y, glutamate metabotropic

receptors, kainate receptor 

PMID: 23996657 [PubMed - in process]

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8/9/2019 @@@@@_____Ascorbate Prevents Cell Death From Prolonged ... [J Neurosci Res

http://slidepdf.com/reader/full/ascorbate-prevents-cell-death-from-prolonged-j-neurosci-res 2/2

17/4/2014 Ascorbate prevents cell death from prolonged ... [J Neurosci Res. 2013] - PubMed - NCBI

http://www.ncbi.nlm.nih.gov/pubmed/23996657 2/2

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