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Age-related decrease of the NMDA receptor-mediated noradrenaline release in rat hippocampus and partial restoration
A Pittaluga1, E Fedele, C Risiglione
1Istituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italy.
European Journal of Pharmacology
|January 26, 1993
Summary
Aging impairs N-methyl-D-aspartate (NMDA)-induced [3H]noradrenaline release in rat hippocampus. However, glycine potentiation of NMDA effects increases with age, suggesting a superresponsive glycine receptor in aged brains.
Area of Science:
- Neuroscience
- Neurochemistry
- Aging Research
Background:
- Age-related cognitive decline is a growing concern.
- Understanding neurotransmitter release changes during aging is crucial for developing interventions.
- N-methyl-D-aspartate (NMDA) receptors play a key role in synaptic plasticity and memory.
Purpose of the Study:
- To investigate the age-dependent changes in [3H]noradrenaline ([3H]NA) release evoked by NMDA in rat hippocampus synaptosomes.
- To examine the effects of glycine and D-cycloserine on NMDA-evoked [3H]NA release in aging rats.
- To explore the underlying mechanisms of altered glycine receptor function in aged brains.
Main Methods:
- Superfusion of rat hippocampus synaptosomes to measure [3H]NA release.
- Application of NMDA, quisqualic acid, and glycine at different concentrations.
- Assessment of K(+)-evoked tritium release from [3H]glycine-prelabeled synaptosomes.
- Comparison of neurotransmitter release and receptor potentiation across different age groups (1.5 to 24 months).
Main Results:
- Maximal NMDA-evoked [3H]NA release significantly decreased with age.
- Quisqualic acid also showed an age-related decline in [3H]NA release, with a different pattern than NMDA.
- Glycine potentiation of NMDA-evoked [3H]NA release increased substantially in aged rats (18-24 months) compared to young rats (1.5 months).
- Glycine uptake was significantly increased, while K(+)-evoked [3H]glycine release was decreased in aged rats, suggesting altered glycine handling.
- D-Cycloserine demonstrated a strong enhancement of NMDA-evoked [3H]NA release.
Conclusions:
- Aging leads to a diminished NMDA-induced noradrenergic release in the hippocampus.
- The aged brain exhibits a superresponsive glycine receptor, potentially compensating for age-related deficits in NMDA function.
- Altered glycine uptake and release mechanisms may contribute to the observed changes in glycine receptor sensitivity.
- D-Cycloserine shows potential therapeutic value for age-related cognitive impairments.