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Impact of chronic doxycycline treatment in the APP/PS1 mouse model of Alzheimer's disease

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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https://www.hal.inserm.fr/inserm-03699325
Contributor : David Blum Connect in order to contact the contributor
Submitted on : Monday, June 20, 2022 - 11:03:58 AM
Last modification on : Friday, June 24, 2022 - 3:40:17 AM

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Victoria Gomez-Murcia, Kevin Carvalho, Bryan Thiroux, Raphaëlle Caillierez, Melanie Besegher, et al.. Impact of chronic doxycycline treatment in the APP/PS1 mouse model of Alzheimer's disease. Neuropharmacology, Elsevier, 2022, 209, pp.108999. ⟨10.1016/j.neuropharm.2022.108999⟩. ⟨inserm-03699325⟩

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