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.
| Original language | English |
|---|---|
| Pages (from-to) | 128-139 |
| Number of pages | 12 |
| Journal | Neurobiology of Aging |
| Volume | 70 |
| DOIs | |
| Publication status | Published - Oct 2018 |
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Doxycycline counteracts neuroinflammation restoring memory in Alzheimer's disease mouse models. / Balducci, Claudia; Santamaria, Giulia; La Vitola, Pietro; Brandi, Edoardo; Grandi, Federica; Viscomi, Arturo Roberto; Beeg, Marten; Gobbi, Marco; Salmona, Mario; Ottonello, Simone; Forloni, Gianluigi.
In: Neurobiology of Aging, Vol. 70, 10.2018, p. 128-139.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Doxycycline counteracts neuroinflammation restoring memory in Alzheimer's disease mouse models
AU - Balducci, Claudia
AU - Santamaria, Giulia
AU - La Vitola, Pietro
AU - Brandi, Edoardo
AU - Grandi, Federica
AU - Viscomi, Arturo Roberto
AU - Beeg, Marten
AU - Gobbi, Marco
AU - Salmona, Mario
AU - Ottonello, Simone
AU - Forloni, Gianluigi
N1 - Copyright © 2018 Elsevier Inc. All rights reserved.
PY - 2018/10
Y1 - 2018/10
N2 - 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.
AB - 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.
U2 - 10.1016/j.neurobiolaging.2018.06.002
DO - 10.1016/j.neurobiolaging.2018.06.002
M3 - Article
C2 - 30007162
VL - 70
SP - 128
EP - 139
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
ER -