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Excitatory amino acid receptor antagonist in murine motoneuron disease (the wobbler mouse)
Abstract:
Recent evidence has suggested a potential role for involvement of excitatory amino acids (EAA) in the pathogenesis of the neuron loss in motoneuron diseases. We have examined the ability of an antagonist of N-methyl-D-aspartate (NMDA) receptors to halt or retard the progression of neurological symptoms in a murine form of motoneuron disease. The wobbler mouse is an autosomal recessive mutant which develops progressive neurological symptoms secondary to motoneuron loss. Treatment of wobbler mice with the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5, 10-imine maleate (MK-801) did not retard neurological deterioration as assessed by a semiquantitative clinical scale. We conclude that NMDA receptor activation is probably not involved in the pathogenesis of motoneuron loss in the wobbler mouse.
Insights
NMDA receptor antagonists, like MK-801, did not prevent neurological decline in wobbler mice, a model for motoneuron disease. This suggests N-methyl-D-aspartate receptor activation is unlikely to cause neuron loss in this condition.
Area of Science:
- Neuroscience
- Pathology
- Pharmacology
Background:
- Excitatory amino acids (EAA) are implicated in motoneuron disease pathogenesis.
- N-methyl-D-aspartate (NMDA) receptors are a key type of EAA receptor.
Purpose of the Study:
- To investigate if blocking NMDA receptors could protect motoneurons.
- To determine the role of NMDA receptor activation in motoneuron loss using the wobbler mouse model.
Main Methods:
- Treatment of wobbler mice with an NMDA receptor antagonist (MK-801).
- Assessment of neurological symptom progression using a semiquantitative clinical scale.
Main Results:
- MK-801 treatment did not slow down or halt neurological deterioration in wobbler mice.
- The drug failed to protect against progressive motoneuron loss.
Conclusions:
- NMDA receptor activation is likely not a primary factor in the pathogenesis of motoneuron loss in the wobbler mouse.
- Targeting NMDA receptors may not be an effective therapeutic strategy for this specific form of motoneuron disease.