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"Memory self-degradation in Alzheimer’s disease and new opportunities for cognitive neuroprotection"тезисы доклада
- Автор: Анохин Константин Владимирович
- Сборник: BIOMEMBRANES 2024 International Conference 7 – 11 October 2024 Book of Abstracts
- Тезисы
- Год издания: 2024
- Место издания: Москва
- Первая страница: 58
- Последняя страница: 58
- Аннотация: Alzheimer's disease (AD) is characterized by dementia - a dramatic damage of already existing old memory. I propose a new hypothesis that this loss is to a large extent due to gradual self-degradation of old memory when it is retrieved in a brain whose ability for reconsolidating is impaired by neurodegeneration. Testing this hypothesis in transgenic 5xFAD mice we found that their contextual memory was impaired following retrieval compared to control animals. To protect memory during reconsolidation, we administered the NMDA receptor antagonist MK-801 which is known to inhibit memory labilization. MK-801 protected memory from deterioration, which confirms our hypothesis. Interestingly, MK-801 had no effect on memory reconsolidation in 2-year-old normal mice, indicating that its effect is specific to amyloid pathology. We then used c-Fos expression mapping of brain activity during contextual memory retrieval following reconsolidation in 5xFAD mice, in normally aged mice, and after MK-801 administration. 5xFAD mice showed increased activation in the frontal cortex and hippocampus compared to control C57 Bl/6 mice. MK-801 increased activity in prelimbic cortex during memory retrieval in all groups. Its protective effect on memory in 5xFAD mice, manifested by increased freezing, was accompanied by increased activation of the amygdala and CA1. This was in contrast to the effect of MK-801 in control mice, where it reduced amygdala activity and impaired memory, as evidenced by reduced freezing. Using the model of retrieval-induce memory impairment we also tested possible protective properties of drugs currently used in the clinic or in clinical trials that have NMDA antagonist properties - riluzole, amantadine andneramexane. We found that each of the drugs tested, when administered systemically before memory reactivation, was able to prevent memory impairment caused by the intracerebral administration of the protein synthesis inhibitor anisomycin. Our work demonstrates a potential new mechanism for an impairment of old memory in Alzheimer's disease and highlights potential strategies to protect this pathology. Supported by RSF 20-15-00283.
- Добавил в систему: Анохин Константин Владимирович