tailieunhanh - báo cáo khoa hoc : Dysregulated Src upregulation of NMDA receptor activity: a common link in chronic pain and schizophrenia

Upregulation ofN-methyl-D-aspartate (NMDA) receptor function by the nonreceptor protein tyrosine kinase Src has been implicated in physiologi-cal plasticity at glutamatergic synapses. Here, we highlight recent findings suggesting that aberrant Src upregulation of NMDA receptors may also be key in pathophysiological conditions. | IFEBS Journal MINIREVIEW Dysregulated Src upregulation of NMDA receptor activity a common link in chronic pain and schizophrenia Michael W. Salter1 2 and Graham M. Pitcher1 2 1 Program in Neurosciences MentalHealth the Hospitalfor Sick Children Toronto ON Canada 2 Department of Physiology University of Toronto Centre for the Study of Pain University of Toronto ON Canada Keywords glutamate receptors hippocampus prefrontal cortex spinal cord dorsal horn synaptic plasticity tyrosine kinase tyrosine phosphatase Correspondence M. W. Salter Program in Neurosciences MentalHealth the Hospitalfor Sick Children Toronto ON M5G 1X8 Canada Fax 416 813 7921 Tel 416 813 6272 E-mail Received 1 July 2011 revised 15 August 2011 accepted 30 August 2011 doi Upregulation of N-methyl-D-aspartate NMDA receptor function by the nonreceptor protein tyrosine kinase Src has been implicated in physiological plasticity at glutamatergic synapses. Here we highlight recent findings suggesting that aberrant Src upregulation of NMDA receptors may also be key in pathophysiological conditions. Within the nociceptive processing network in the dorsal horn of the spinal cord pathologically increased Src upregulation of NMDA receptors is critical for pain hypersensitivity in models of chronic inflammatory and neuropathic pain. On the other hand in the hippocampus and prefrontal cortex the physiological upregulation of NMDA receptors by Src is blocked by neuregulin 1-ErbB4 signaling a pathway that is genetically implicated in the positive symptoms of schizophrenia. Thus either over-upregulation or under-upregulation of NMDA receptors by Src may lead to pathological conditions in the central nervous system. Therefore normalizing Src upregulation of NMDA receptors may be a novel therapeutic approach for central nervous system disorders without the deleterious consequences of directly blocking NMDA receptors. Introduction N-methyl-D-aspartate NMDA .

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