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The neuroprotective agent memantine induces brain-derived neurotrophic factor and trkB receptor expression in rat
M Marvanová1, M Lakso, J Pirhonen
1A. I. Virtanen Institute, University of Kuopio, Kuopio, 70211, Finland.
Abstract:
Memantine is a medium-affinity uncompetitive N-methyl-d-aspartate receptor antagonist and has been clinically used as a neuroprotective agent to treat Alzheimer's and Parkinson's diseases. We have examined the effect of memantine (ip 5-50 mg/kg; 4 h) on the expression of brain-derived neurotrophic factor (BDNF) and trkB receptor mRNAs in rat brain by in situ hybridization. Memantine at a clinically relevant dose markedly increased BDNF mRNA levels in the limbic cortex, and this effect was more widespread and pronounced at higher doses. Effects of memantine on BDNF mRNA were also reflected in changes in BDNF protein levels. Moreover, memantine induced isoforms of the BDNF receptor trkB. Taken together, these data suggest that the neuroprotective properties of memantine could be mediated by the increased endogenous production of BDNF in the brain. These findings may open up new possibilities of pharmacologically regulating the expression of neurotrophic factors in the brain.
Insights
Memantine treatment significantly boosts brain-derived neurotrophic factor (BDNF) and its receptor (trkB) in rats. This suggests memantine
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Memantine is an N-methyl-d-aspartate receptor antagonist used for Alzheimer's and Parkinson's diseases.
- Its neuroprotective mechanisms are not fully understood.
- Brain-derived neurotrophic factor (BDNF) plays a crucial role in neuronal survival and function.
Purpose of the Study:
- To investigate the effect of memantine on the expression of BDNF and its receptor, trkB.
- To explore the potential role of BDNF in memantine's neuroprotective effects.
Main Methods:
- Rats were administered memantine at doses of 5-50 mg/kg.
- In situ hybridization was used to examine BDNF and trkB mRNA expression in rat brain.
- BDNF protein levels were also assessed.
Main Results:
- Memantine significantly increased BDNF mRNA levels in the limbic cortex, dose-dependently.
- Increased BDNF mRNA correlated with elevated BDNF protein levels.
- Memantine also induced isoforms of the BDNF receptor, trkB.
Conclusions:
- Memantine enhances endogenous BDNF production and trkB receptor expression in the brain.
- These changes in neurotrophic factors may underlie memantine's neuroprotective properties.
- This study highlights a potential pathway for pharmacologically modulating neurotrophic factors.