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The NMDA receptor contributes to anoxic aglycemic induced irreversible inhibition of synaptic transmission
Abstract:
Percent recovery of CA1 field EPSP amplitude following various anoxic aglycemic (AA) periods was examined in rat hippocampal slices superfused with MK-801 (0.1 microM, 1 microM, 10 microM) or Mg(2+)-free artificial cerebrospinal fluid. Slices treated with 0.1 microM MK-801 showed greater percent recuperation of EPSP amplitude following 3 min 30 s of AA (36 +/- 12% vs 6 +/- 4% in controls). Higher concentrations of MK-801 resulted in a greater recovery of EPSP amplitudes in more than one time period of AA, with 10 microM MK-801 providing protection in up to 4 min 30 s AA. Percent recuperation of EPSP amplitude was smaller in Mg(2+)-free slices following 2 min (34 +/- 15% vs 81 +/- 11% in controls) and 2 min 30 (25 +/- 14% vs 77 +/- 10% in controls) of AA. These results suggest that the activation of the N-methyl-D-aspartate (NMDA) receptor channel may contribute to irreversible AA induced synaptic failure in CA1.
Insights
MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, protected against irreversible anoxic-aglycemic (AA) induced synaptic failure in rat hippocampus. This suggests NMDA receptor channel activation contributes to synaptic damage during oxygen deprivation.
Area of Science:
- Neuroscience
- Neurophysiology
- Cellular Neuroscience
Background:
- Anoxic-aglycemic (AA) conditions can lead to irreversible synaptic failure.
- The role of N-methyl-D-aspartate (NMDA) receptor activation in this process requires further elucidation.
Purpose of the Study:
- To investigate the neuroprotective effects of MK-801, an NMDA receptor antagonist, against AA-induced synaptic damage in rat hippocampal slices.
- To determine the involvement of NMDA receptor channel activity in irreversible synaptic failure.
Main Methods:
- Rat hippocampal slices were subjected to varying durations of AA.
- Slices were superfused with different concentrations of MK-801 (0.1, 1, 10 microM) or Mg(2+)-free artificial cerebrospinal fluid.
- Recovery of CA1 field excitatory postsynaptic potential (EPSP) amplitude was measured.
Main Results:
- MK-801 at 0.1 microM significantly improved EPSP amplitude recovery after 3 min 30 s of AA compared to controls.
- Higher MK-801 concentrations (up to 10 microM) provided protection for longer AA durations (up to 4 min 30 s).
- Mg(2+)-free conditions impaired EPSP recovery, indicating the role of NMDA receptor-mediated excitotoxicity.
Conclusions:
- NMDA receptor channel activation contributes to irreversible synaptic failure induced by AA in the CA1 region.
- MK-801 demonstrates neuroprotective potential against excitotoxic damage during oxygen-glucose deprivation.