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Effects of Memantine on the Spontaneous Firing Frequency of Hippocampal CA1 Pyramidal Neurons in Intact and Alzheimer
Nastaran Zamani1, Ahmad Ali Moazedi2,3, Mohamad Reza Afarinesh Khaki4
1Department of Biology, School of Science, Payame Noor University, Tehran, Iran.
Introduction:
Memantine (MEM) is a noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist clinically used for the treatment of Alzheimer disease (AD) in mild to severe conditions. The present study was conducted to investigate the effects of memantine on the spontaneous firing frequency of CA1 pyramidal neurons in rats caused by an electrical lesion of Nucleus Basalis Magnocellularis (NBM). Then, this model of AD rats was compared with the intact adult male rats.
Methods:
In this study, adult male rats were divided into two groups. Group I (lesion of NBM, n=53) includes the following subgroups: lesion+saline, sham+saline, lesion+MEM 5 mg/kg, lesion+MEM 10 mg/kg, and lesion+MEM 20mg/kg. Group II (intact, n=48) includes the following subgroups: intact+saline, intact+MEM 3mg/kg, intact+MEM 5mg/kg, and intact+MEM 10mg/kg. Extracellular single-unit recording (15 min baseline+105 min after MEM or saline) was performed under urethane-anesthetized rats.
Results:
The results showed that the mean frequency of CA1 pyramidal neurons after saline in the lesion+saline (P<0.001) group significantly decreases compared with the intact+saline and sham+saline groups. In addition, after saline and memantine, the mean frequency of CA1 pyramidal neurons in the lesion+MEM 10 mg/kg (P<0.01) and lesion+MEM 20 mg/kg (P<0.001) groups significantly increased compared with the lesion+saline group. Also, the mean frequencies of CA1 pyramidal neurons in the intact+MEM 10 mg/kg (P<0.001) group significantly decreased compared with the intact+saline group.
Conclusion:
Results showed that memantine increases the electrical activity of CA1 pyramidal neurons in a rat model of AD. Furthermore, in the intact adult male rats, the low-dose memantine, contrary to high dose, does not decrease the electrical activity of CA1 pyramidal neurons.
Insights
Memantine (MEM) increases CA1 pyramidal neuron activity in a rat model of Alzheimer disease (AD). In healthy rats, low-dose MEM did not decrease neuronal activity, unlike higher doses.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Memantine (MEM) is an N-methyl-D-aspartate receptor (NMDAR) antagonist used for Alzheimer disease (AD).
- Investigating MEM's effect on CA1 pyramidal neurons is crucial for understanding its therapeutic mechanisms.
Purpose of the Study:
- To examine the impact of memantine on CA1 pyramidal neuron firing frequency in a rat model of AD.
- To compare these effects with those in intact adult male rats.
Main Methods:
- Adult male rats were divided into two groups: NBM-lesioned (AD model) and intact.
- Different doses of MEM or saline were administered.
- Extracellular single-unit recordings were performed under urethane anesthesia.
Main Results:
- In the AD model, higher doses of MEM (10 and 20 mg/kg) significantly increased CA1 pyramidal neuron firing frequency compared to saline.
- In intact rats, a high dose of MEM (10 mg/kg) significantly decreased neuronal firing frequency.
- Saline administration in the lesioned group significantly decreased neuronal firing frequency compared to intact and sham groups.
Conclusions:
- Memantine enhances the electrical activity of CA1 pyramidal neurons in a rat model of AD.
- In intact rats, low-dose memantine does not reduce neuronal electrical activity, contrasting with higher doses.
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