Neuronal Hyperexcitability in APPSWE/PS1dE9 Mouse Models of Alzheimer’s Disease
| Autor: | Rüdiger Köhling, Angela Kuhla, Timo Kirschstein, Stefan J. Teipel, Luisa Müller |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Amyloid APPswe/PS1dE9 mice genetics [Alzheimer Disease] Disease amyloid-β Biology physiopathology [Alzheimer Disease] Amyloid beta-Protein Precursor Mice 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Presenilin-1 medicine Animals ddc:610 Neurons General Neuroscience Amyloidosis genetics [Presenilin-1] General Medicine physiology [Neurons] medicine.disease Appswe ps1de9 neuronal hyperexcitability Disease Models Animal Psychiatry and Mental health Clinical Psychology Electrophysiology 030104 developmental biology genetics [Amyloid beta-Protein Precursor] Neuronal Hyperexcitability Glymphatic system Geriatrics and Gerontology Alzheimer’s disease Neuroscience sleep-wake cycle 030217 neurology & neurosurgery |
| Zdroj: | Journal of Alzheimer's disease 81(3), 855-869 (2021). doi:10.3233/JAD-201540 |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-201540 |
| Popis: | Transgenic mouse models serve a better understanding of Alzheimer’s disease (AD) pathogenesis and its consequences on neuronal function. Well-known and broadly used AD models are APPswe/PS1dE9 mice, which are able to reproduce features of amyloid-β (Aβ) plaque formations as well as neuronal dysfunction as reflected in electrophysiological recordings of neuronal hyperexcitability. The most prominent findings include abnormal synaptic function and synaptic reorganization as well as changes in membrane threshold and spontaneous neuronal firing activities leading to generalized excitation-inhibition imbalances in larger neuronal circuits and networks. Importantly, these findings in APPswe/PS1dE9 mice are at least partly consistent with results of electrophysiological studies in humans with sporadic AD. This underscores the potential to transfer mechanistic insights into amyloid related neuronal dysfunction from animal models to humans. This is of high relevance for targeted downstream interventions into neuronal hyperexcitability, for example based on repurposing of existing antiepileptic drugs, as well as the use of combinations of imaging and electrophysiological readouts to monitor effects of upstream interventions into amyloid build-up and processing on neuronal function in animal models and human studies. This article gives an overview on the pathogenic and methodological basis for recording of neuronal hyperexcitability in AD mouse models and on key findings in APPswe/PS1dE9 mice. We point at several instances to the translational perspective into clinical intervention and observation studies in humans. We particularly focus on bi-directional relations between hyperexcitability and cerebral amyloidosis, including build-up as well as clearance of amyloid, possibly related to sleep and so called glymphatic system function. |
| Databáze: | OpenAIRE |
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