Iron is a potential key mediator of glutamate excitotoxicity in spinal cord motor neurons

Brain Research
Jixu YuChunyan Li

Abstract

Threohydroxyaspartate (THA)-induced glutamate excitotoxicity in organotypic culture of rat spinal cord is a well-known model of motor neuron degeneration. THA causes accumulation of synaptic glutamate and over stimulation of the postsynaptic receptor by inhibiting glutamate uptake. This model has also been used to identify agents that inhibit glutamate excitotoxicity by increasing the expression of glutamate transporter. We now show that THA also increases iron level in rat spinal cord tissue, with concomitant modulation of key iron transport and storage proteins, including transferrin receptor, divalent metal-ion transporter 1 and ferritin. More significantly, iron chelator deferoxamine (DFO) was able to completely prevent THA-induced motor neuron degeneration. The protective effect of DFO did not involve enhancing glutamate uptake. These data provide new mechanistic insight into THA-induced glutamate excitotoxicity and suggest that blocking THA-induced iron rise alone may be sufficient for prevention of glutamate excitotoxicity.

References

Nov 30, 1995·Biochimica Et Biophysica Acta·Z M Qian, P L Tang
Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·J D RothsteinR W Kuncl
Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·M A SmithG Perry
Oct 29, 1998·Biochemical and Biophysical Research Communications·F Kishi, M Tabuchi
Oct 16, 1999·The American Journal of the Medical Sciences·D H Boldt
May 5, 2000·Journal of Neurology·V SilaniG Scarlato
May 9, 2006·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Ruth DanzeisenMaria Teresa Carrì
Dec 23, 2006·Science·Tracey A Rouault

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Citations

Jan 9, 2014·ASN Neuro·Kelsey J WeigelSteven M Levine
Jul 9, 2014·Nature Reviews. Neurology·Erin StephensonV Wee Yong
Apr 8, 2010·Free Radical Research·Irene PaternitiSalvatore Cuzzocrea
Oct 19, 2011·Journal of Neurochemistry·Rachel WilliamsSteven M LeVine
Oct 31, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Scott AytonAshley I Bush
Nov 7, 2019·Journal of Neurochemistry·Israel C NnahMarianne Wessling-Resnick
Dec 13, 2018·Neural Regeneration Research·Xue YaoShi-Qing Feng
Sep 16, 2017·Acta Biochimica Et Biophysica Sinica·Ying TianXiaobo Xia
Jun 6, 2018·Journal of Alzheimer's Disease : JAD·Darius J R LaneAshley I Bush
Nov 28, 2018·Pharmaceuticals·Israel C Nnah, Marianne Wessling-Resnick
Jul 6, 2017·Molecular Medicine Reports·Fengyuan CheYifeng Du

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