Long-term caffeine treatment of Alzheimer mouse models ameliorates behavioural deficits and neuron loss and promotes cellular and molecular markers of neurogenesis
| Autor: | Martina Stazi, Sandra Lehmann, M. Sadman Sakib, Tonatiuh Pena-Centeno, Luca Büschgens, Andre Fischer, Sascha Weggen, Oliver Wirths |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Amyloid Neurogenesis metabolism [Amyloid beta-Peptides] Plaque Amyloid drug effects [Neurogenesis] Cellular and Molecular Neuroscience Mice pharmacology [Caffeine] Alzheimer Disease Caffeine drug therapy [Plaque Amyloid] drug therapy [Alzheimer Disease] drug effects [Neurons] pathology [Neurons] Animals Transgenic mice ddc:610 Molecular Biology Cells Cultured Pharmacology Neurons Behavior Tg4-42 Amyloid beta-Peptides RNA sequencing Cell Biology 5xFAD Mice Inbred C57BL Molecular Medicine Female Original Article Transcriptome Alzheimer’s disease Biomarkers metabolism [Biomarkers] |
| Zdroj: | Cellular and Molecular Life Sciences Cellular and molecular life sciences 79(1), 55 (2021). doi:10.1007/s00018-021-04062-8 |
| ISSN: | 1420-9071 |
| DOI: | 10.1007/s00018-021-04062-8 |
| Popis: | Epidemiological studies indicate that the consumption of caffeine, the most commonly ingested psychoactive substance found in coffee, tea or soft drinks, reduces the risk of developing Alzheimer’s disease (AD). Previous treatment studies with transgenic AD mouse models reported a reduced amyloid plaque load and an amelioration of behavioral deficits. It has been further shown that moderate doses of caffeine have the potential to attenuate the health burden in preclinical mouse models of a variety of brain disorders (reviewed in Cunha in J Neurochem 139:1019–1055, 2016). In the current study, we assessed whether long-term caffeine consumption affected hippocampal neuron loss and associated behavioral deficits in the Tg4-42 mouse model of AD. Treatment over a 4-month period reduced hippocampal neuron loss, rescued learning and memory deficits, and ameliorated impaired neurogenesis. Neuron-specific RNA sequencing analysis in the hippocampus revealed an altered expression profile distinguished by the up-regulation of genes linked to synaptic function and processes, and to neural progenitor proliferation. Treatment of 5xFAD mice, which develop prominent amyloid pathology, with the same paradigm also rescued behavioral deficits but did not affect extracellular amyloid-β (Aβ) levels or amyloid precursor protein (APP) processing. These findings challenge previous assumptions that caffeine is anti-amyloidogenic and indicate that the promotion of neurogenesis might play a role in its beneficial effects. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-021-04062-8. |
| Databáze: | OpenAIRE |
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