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Updated: Jun 26, 2026

Using Enzyme-based Biosensors to Measure Tonic and Phasic Glutamate in Alzheimer's Mouse Models
Published on: May 3, 2017
Iron is a potential key mediator of glutamate excitotoxicity in spinal cord motor neurons
Jixu Yu1, Yansu Guo, Mengmeng Sun
1Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
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.
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