TY - JOUR
T1 - Blockade of desensitization augments quisqualate excitotoxicity in hippocampal neurons
AU - Zorumski, Charles F.
AU - Thio, Liu Lin
AU - Clark, Gary D.
AU - Clifford, David B.
N1 - Funding Information:
This work was supported in part by Physician Scientist Award MH00630, the Klingenstein Foundation, the Bantly Foundation, MH45493, and DA05072. G. D. C. was an American Academy of Neurology postdoctoral fellow. Th~ authors thank Drs. J. W. OI-ney and J. Yang for comments and many helpful discussions.
PY - 1990/7
Y1 - 1990/7
N2 - Glutamate neurotoxicity is thought to play a role in the pathogenesis of several neurodegenerative diseases. While prolonged activation of either NMDA or non-NMDA receptors causes neuronal damage, NMDA receptors appear to mediate most of the glutamate toxicity. The reasons why NMDA toxicity predominates are uncertain but may relate to more effective neuroprotective mechanisms acting at non-NMDA receptors. To determine whether desensitization is one such mechanism, we studied the effects of the lectin wheat germ agglutinin (WGA) on quisqualate currents and toxicity in cultured postnatal rat hippocampal neurons. After WGA treatment, quisqualate currents exhibit little desensitization and a 4- to 8-fold increase in steady-state amplitude. WGA also markedly augments the degree of acute, quisqualate-induced neuronal degeneration. These results suggest that non-NMDA desensitization serves a neuroprotective function in hippocampal neurons.
AB - Glutamate neurotoxicity is thought to play a role in the pathogenesis of several neurodegenerative diseases. While prolonged activation of either NMDA or non-NMDA receptors causes neuronal damage, NMDA receptors appear to mediate most of the glutamate toxicity. The reasons why NMDA toxicity predominates are uncertain but may relate to more effective neuroprotective mechanisms acting at non-NMDA receptors. To determine whether desensitization is one such mechanism, we studied the effects of the lectin wheat germ agglutinin (WGA) on quisqualate currents and toxicity in cultured postnatal rat hippocampal neurons. After WGA treatment, quisqualate currents exhibit little desensitization and a 4- to 8-fold increase in steady-state amplitude. WGA also markedly augments the degree of acute, quisqualate-induced neuronal degeneration. These results suggest that non-NMDA desensitization serves a neuroprotective function in hippocampal neurons.
UR - http://www.scopus.com/inward/record.url?scp=0025356566&partnerID=8YFLogxK
U2 - 10.1016/0896-6273(90)90033-C
DO - 10.1016/0896-6273(90)90033-C
M3 - Article
C2 - 2164404
AN - SCOPUS:0025356566
SN - 0896-6273
VL - 5
SP - 61
EP - 66
JO - Neuron
JF - Neuron
IS - 1
ER -