Neural Regeneration Research ›› 2022, Vol. 17 ›› Issue (10): 2208-2210.doi: 10.4103/1673-5374.335793

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N-methyl-D-aspartate receptor functions altered by neuronal PTP1B activation in Alzheimer’s disease and schizophrenia models

Alexandre F. R. Stewart, Hsiao-Huei Chen   

  1. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, and University of Ottawa Heart Institute, Ottawa, ON, Canada (Stewart AFR) 
    Centre for Infection, Immunity and Inflammation, Ottawa, ON, Canada (Stewart AFR, Chen HH)
    Medicine, Cellular and Molecular Medicine, University of Ottawa Brain and Mind Institute, Ottawa Hospital Research Institute, Ottawa, ON, Canada (Chen HH) 
  • Online:2022-10-15 Published:2022-03-16
  • Contact: Alexandre F. R. Stewart, PhD, astewart@ottawaheart.ca; Hsiao-Huei Chen, PhD, hchen@uottawa.ca.
  • Supported by:
    This work was supported by grants from the Heart and Stroke Foundation of Canada (G-13-0002596 & G-18-0022157, to HHC; G-16-00014085, to AFRS), Ontario Mental Health Foundation (to HHC), the Canadian Institutes of Health Research (201610PJT #376403, to HHC; 201610PJT #376503, to AFRS), the Natural Science and Engineering Research Council of Canada (RGPIN/06212-2014, to HHC; RGPIN/2016-04985, to AFRS). HHC is also supported by a Mid-Career Investigator Award (grant # 7506) from the Heart and Stroke Foundation of Ontario. 

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Abstract: Glutamate is the main excitatory neurotransmitter in the brain and binds to two major classes of receptors, the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and the N-methyl-D-aspartate (NMDA) receptors. Unlike AMPA receptors that are immediately activated by glutamate release, NMDA receptors are blocked by magnesium and can only be activated by glutamate after membrane depolarization. Thus, NMDA receptors are only activated after repeated AMPA receptor activation by glutamate. NMDA receptors are, for the most part, calcium-permeable channels. Calcium influx through NMDA receptors modulates synaptic transmission in neurons based on prior history of excitation, and provides a means of scaling the strength of synapses required for Hebbian plasticity. NMDA receptors were first characterized in the post-synaptic membrane, where calcium influx controls AMPA receptor levels and activity-dependent gene expression. Tyrosine phosphorylation of postsynaptic NMDA receptors promotes calcium influx, whereas dephosphorylation of NMDA receptors causes their internalization and reduces calcium influx through NMDA receptors (Wang and Salter, 1994). More than 10 years ago, the striatal-enriched tyrosine phosphatase Step61 was tied to NMDA receptor dephosphorylation in the context of Alzheimer’s disease and amyloid-beta (Kurup et al., 2010).