Abstract |
Due to the pathophysiological complexity of Alzheimer's disease, multitarget approaches able to mitigate several pathogenic mechanisms are of interest. Previous studies have pointed to the neuroprotective potential of Doxycycline (Dox), a safe and inexpensive second-generation tetracycline. Dox has been particularly reported to slow down aggregation of misfolded proteins but also to mitigate neuroinflammatory processes. Here, we have evaluated the pre-clinical potential of Dox in the APP/PS1 mouse model of amyloidogenesis. Dox was provided to APP/PS1 mice from the age of 8 months, when animals already exhibit amyloid pathology and memory deficits. Spatial memory was then evaluated from 9 to 10 months of age. Our data demonstrated that Dox moderately improved the spatial memory of APP/PS1 mice without exerting major effect on amyloid lesions. While Dox did not alleviate overall glial reactivity, we could evidence that it rather enhanced the amyloid-dependent upregulation of several neuroinflammatory markers such as CCL3 and CCL4. Finally, Dox exerted differentially regulated the levels of synaptic proteins in the hippocampus and the cortex of APP/PS1 mice. Overall, these observations support that chronic Dox delivery does not provide major pathophysiological improvements in the APP/PS1 mouse model.
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Authors | Victoria Gomez-Murcia, Kevin Carvalho, Bryan Thiroux, Raphaëlle Caillierez, Melanie Besegher, Nicolas Sergeant, Luc Buée, Emile Faivre, David Blum |
Journal | Neuropharmacology
(Neuropharmacology)
Vol. 209
Pg. 108999
(05 15 2022)
ISSN: 1873-7064 [Electronic] England |
PMID | 35181375
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2022 Elsevier Ltd. All rights reserved. |
Chemical References |
- Amyloid beta-Peptides
- Amyloid beta-Protein Precursor
- Presenilin-1
- Doxycycline
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Topics |
- Alzheimer Disease
(metabolism)
- Amyloid beta-Peptides
(metabolism)
- Amyloid beta-Protein Precursor
(genetics, metabolism)
- Animals
- Disease Models, Animal
- Doxycycline
(pharmacology, therapeutic use)
- Hippocampus
(metabolism)
- Mice
- Mice, Transgenic
- Presenilin-1
(genetics, metabolism)
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