Effects of Memantine on Neuronal Structure and Conditioned Fear in the Tg2576 Mouse Model of Alzheimer's Disease
| Autor: | Carla M. Yuede, Carolyn A. Coughlan, John G. Csernansky, Brian A. Lewis, Hongxin Dong |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Genotype Neurotoxins Hippocampus Mice Transgenic Plaque Amyloid Neuroprotection Article Mice Microscopy Electron Transmission Alzheimer Disease Memantine Internal medicine Conditioning Psychological medicine Animals Pharmacology Behavior Animal Dose-Response Relationship Drug business.industry Antagonist Glutamate receptor Brain Fear medicine.disease Axons Mice Inbred C57BL Disease Models Animal Psychiatry and Mental health Neuroprotective Agents Endocrinology Mechanism of action Synapses NMDA receptor medicine.symptom Alzheimer's disease Wallerian Degeneration business Excitatory Amino Acid Antagonists medicine.drug |
| Zdroj: | Neuropsychopharmacology. 33:3226-3236 |
| ISSN: | 1740-634X 0893-133X |
| DOI: | 10.1038/npp.2008.53 |
| Popis: | Memantine, an uncompetitive NMDA receptor antagonist used for the treatment of Alzheimer's disease (AD), has been hypothesized to have neuroprotective properties. However, the similarity of its mechanism of action to other NMDA receptor antagonists has led to concerns that it may also have neurotoxic effects. To assess both the neuroprotective and neurotoxic potential of memantine in a mouse model of AD (Tg2576 mice), we used quantitative light and electron microscopy to investigate the effects of long-term (6 months) administration of memantine (5, 10 and 20 mg/kg) on plaque deposition and neuronal morphology in the hippocampus and overlying cortex. A fear-conditioning paradigm was used to evaluate the behavioral consequences of any observed changes in structure. Administration of the two higher doses of memantine (10 and 20 mg/kg) was associated with a significant decrease in beta-amyloid (Abeta) plaque deposition, increases in synaptic density and the appearance of degenerating axons; the latter two effects were independent of genotype. Administration of the lowest dose of memantine (5 mg/kg) was associated with a significant decrease in Abeta plaque deposition and a significant increase in synaptic density, but not a significant increase in degenerating axons. However, memantine did not significantly improve behavioral deficits associated with genotype in a fear-conditioning paradigm at any dose. These results suggest that chronic memantine administration may have both neuroprotective and neurotoxic effects in a mouse model of AD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|