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Aging and the effects of MK-801 on anoxic damage in rat hippocampal slices
E L Roberts1, D Wisotzky, C P Chih
1Geriatric Research, Education, and Clinical Center, Miami VA Medical Center, Miami, FL 33125, USA.
Abstract:
We examined whether age-related differences in N-methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity contribute to the increased vulnerability of the aged brain to anoxic damage. In both adult and aged hippocampal slices, NMDA receptor blockade with MK-801 did not affect the onset of anoxic depolarization. MK-801 improved the postanoxic recovery of synaptic transmission by the same percentage in both age groups. Thus, the faster onset of anoxic depolarization and diminished postanoxic recovery of synaptic transmission seen in aged hippocampal slices cannot be attributed to age-related differences in NMDA receptor-mediated neurotoxicity.
Insights
Age-related brain vulnerability to oxygen deprivation is not due to differences in N-methyl-D-aspartate (NMDA) receptor neurotoxicity. NMDA receptor blockade did not alter anoxic damage onset or recovery in adult versus aged hippocampal slices.
Area of Science:
- Neuroscience
- Aging Research
- Neurotoxicity
Background:
- The aged brain exhibits increased vulnerability to anoxic damage.
- N-methyl-D-aspartate (NMDA) receptors are implicated in excitotoxicity and neuronal damage.
Purpose of the Study:
- To investigate if age-related differences in NMDA receptor-mediated neurotoxicity contribute to heightened susceptibility of aged brains to anoxic injury.
- To determine the role of NMDA receptors in the differential response to anoxia between adult and aged hippocampal tissues.
Main Methods:
- Experiments were conducted using adult and aged hippocampal slices.
- NMDA receptor function was blocked using the antagonist MK-801.
- The onset of anoxic depolarization and the recovery of synaptic transmission post-anoxia were measured.
Main Results:
- NMDA receptor blockade with MK-801 did not alter the onset of anoxic depolarization in either adult or aged hippocampal slices.
- MK-801 administration resulted in a similar percentage improvement in postanoxic synaptic transmission recovery across both age groups.
- The observed age-related differences in anoxic depolarization onset and recovery are not explained by NMDA receptor neurotoxicity.
Conclusions:
- Age-related differences in NMDA receptor-mediated neurotoxicity do not account for the increased vulnerability of the aged brain to anoxic damage.
- The findings suggest that other mechanisms underlie the heightened sensitivity of aged hippocampal tissue to oxygen deprivation.
- Targeting NMDA receptors may not be a viable strategy to mitigate age-related anoxic brain injury.