Doxycycline counteracts neuroinflammation restoring memory in Alzheimer's disease mouse models.

Abstract

β-Amyloid oligomers (AβOs) and neuroinflammation are 2 main culprits to counteract in Alzheimer's disease (AD). Doxycycline (DOXY) is a second generation antibiotic of the tetracycline class that are promising drugs tested in many clinical trials for a number of different pathologies. DOXY is endowed with antiamyloidogenic properties and better crosses the blood-brain barrier, but its efficacy has never been tested in AD mice. We herein show that 15- to 16-month-old APP/PS1dE9 (APP/PS1) AD mice receiving DOXY under different treatment regimens recovered their memory without plaque reduction. An acute DOXY treatment was, also, sufficient to improve APP/PS1 mouse memory, suggesting an action against soluble AβOs. This was confirmed in an AβO-induced mouse model, where the AβO-mediated memory impairment was abolished by a DOXY pretreatment. Although AβOs induce memory impairment through glial activation, assessing the anti-inflammatory action of DOXY, we found that in both the AβO-treated and APP/PS1 mice, the memory recovery was associated with a lower neuroinflammation. Our data promote DOXY as a hopeful repositioned drug counteracting crucial neuropathological AD targets.

• Authors: Claudia Balducci, Giulia Santamaria, Pietro La Vitola, Edoardo Brandi, Federica Grandi, Arturo Roberto Viscomi, Marten Beeg, Marco Gobbi, Mario Salmona, Simone Ottonello, Gianluigi Forloni
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 70 Pg. 128-139 (10 2018) ISSN: 1558-1497 [Electronic] United States
• PMID: 30007162 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Anti-Bacterial Agents
• Anti-Inflammatory Agents, Non-Steroidal
• Doxycycline

Topics

• Alzheimer Disease (complications, pathology, psychology)
• Amyloid beta-Peptides (metabolism)
• Animals
• Anti-Bacterial Agents (administration & dosage)
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage)
• Brain (drug effects, pathology)
• Disease Models, Animal
• Doxycycline (administration & dosage)
• Drug Repositioning
• Encephalitis (complications, drug therapy, pathology)
• Male
• Memory (drug effects)
• Mice, Inbred C57BL
• Mice, Transgenic
• Plaque, Amyloid (pathology)