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Chronic neonatal NMDA blockade results in long-term cholinergic increase in the rat spinal cord
M Virgili1, F Facchinetti, A Contestabile
1Department of Biology, University of Bologna, Italy.
Insights
Neonatal treatment with an N-methyl-D-aspartate (NMDA) antagonist increased choline acetyltransferase in adult rat spinal cords. This suggests NMDA receptors play a developmental role in the spinal cord.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- N-methyl-D-aspartate (NMDA) receptors are crucial for synaptic plasticity and neuronal development.
- Understanding the role of NMDA receptors during development is essential for identifying potential therapeutic targets.
Purpose of the Study:
- To investigate the long-term effects of neonatal NMDA receptor blockade on spinal cord neurochemistry in rats.
- To explore the developmental role of NMDA receptors in the central nervous system.
Main Methods:
- Rat pups were administered increasing doses of CGP 39551, a competitive NMDA antagonist, from postnatal day 1 to 22.
- Control groups included normal rats and neonatally undernourished rats.
- Adult spinal cord tissue was analyzed for neurochemical markers, including choline acetyltransferase and glutamate uptake.
Main Results:
- Neonatal NMDA antagonist treatment led to a significant 14% increase in choline acetyltransferase in adult spinal cords.
- High-affinity glutamate uptake was also increased in treated rats, an effect also observed in neonatally undernourished rats.
- No significant alterations were found in other neurochemical markers.
Conclusions:
- Neonatal NMDA receptor blockade influences spinal cord development, specifically affecting cholinergic systems.
- These findings support a developmental role for NMDA receptors extending to the spinal cord.
- Chronic neonatal NMDA receptor blockade models may be valuable for studying neurodevelopmental processes.
Abstract:
Rat pups were treated daily with increasing doses of the competitive N-methyl-D-aspartate (NMDA) antagonist CGP 39551 from postnatal day 1 to 22. Normal rats, as well as rats kept undernourished to the same extent as CGP 39551-treated animals were raised in parallel. The neonatal treatment resulted in significant increase of choline acetyltransferase (+14%) in the adult spinal cord. High affinity glutamate uptake was increased to a similar magnitude in treated rats, but the same effect was also noticed for neonatally undernourished rats. No alteration of other neurochemical markers was observed. The present results add new evidence to a developmental role mediated by NMDA receptors and extend to the spinal cord the value of models of chronic neonatal block of this receptor.