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General Information:
Id:
1,317
Diseases:
Amyotrophic lateral sclerosis
Mus musculus
SOD1G93A transgenic mouse, transfected with human SOD1G93A
article
Reference:
Yang Y et al.(2009) Presynaptic regulation of astroglial excitatory neurotransmitter transporter GLT1 Neuron 61: 880-894
[PMID: 19323997]
Interaction Information:
Comment
Astroglia regulate synaptic glutamate, via neurotransmitter transport by GLT1/EAAT2. Similar to the acute corticospinal lesion experiments and ricin toxin lesion, the loss of GLT1 protein in rodent models of ALS is focal to the region of degenerating motor neurons and spreads along the lumbar spinal cord.
Quantitative real time PCR analysis of GLT1 mRNA from lumbar spinal cord of SOD1G93A mice at different stage of disease progression (60, 90, 120d) showed that GLT1 mRNA was reduced to 65% of control at disease onset and further decreased to 40% of control as disease progressed to end stage.
The GLT1 promoter activity was analysed in GLT1 BAC eGFP reporter mice. Presynaptic terminals regulate astroglial synaptic GLT1/EAAT2, via kappa B-motif binding phosphoprotein (KBBP, the mouse homologue of human HNRNPK), which binds the GLT1/EAAT2 promoter. Neuron-stimulated KBBP is required for GLT1/EAAT2 transcriptional activation and is responsible for astroglial alterations in neural injury.
Elevated levels of glutamate are closely associated with loss of EAAT2 in chronic neurological injuries including ALS, Huntington's disease, and multiple sclerosis.
Elevated levels of glutamate are closely associated with loss of EAAT2 in chronic neurological injuries including ALS, Huntington's disease, and multiple sclerosis.
Elevated levels of glutamate are closely associated with loss of EAAT2 in chronic neurological injuries including ALS, Huntington's disease, and multiple sclerosis.
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