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Low-Dose Phosphodiesterase III Inhibitor Reduces the Vascular Amyloid Burden in Amyloid-β Protein Precursor Transgenic Mice

A previous study reported that relatively high-dose cilostazol (0.3%) promoted the drainage of cerebrovascular amyloid-β (Aβ) protein in Aβ Precursor Protein (APP) transgenic mice overexpressing vasculotropic Aβ. We investigated whether lower-dose cilostazol can decrease micro-hemorrhages and Aβ dep...

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Autores principales: Yakushiji, Yusuke, Kawamoto, Kazuhiro, Uchihashi, Kazuyoshi, Ihara, Masafumi, Aoki, Shigehisa, Nagaishi, Yukiko, Suzuyama, Kohei, Tsugitomi, Yumiko, Hara, Hideo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177305/
https://www.ncbi.nlm.nih.gov/pubmed/32225099
http://dx.doi.org/10.3390/ijms21072295
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author Yakushiji, Yusuke
Kawamoto, Kazuhiro
Uchihashi, Kazuyoshi
Ihara, Masafumi
Aoki, Shigehisa
Nagaishi, Yukiko
Suzuyama, Kohei
Tsugitomi, Yumiko
Hara, Hideo
author_facet Yakushiji, Yusuke
Kawamoto, Kazuhiro
Uchihashi, Kazuyoshi
Ihara, Masafumi
Aoki, Shigehisa
Nagaishi, Yukiko
Suzuyama, Kohei
Tsugitomi, Yumiko
Hara, Hideo
author_sort Yakushiji, Yusuke
collection PubMed
description A previous study reported that relatively high-dose cilostazol (0.3%) promoted the drainage of cerebrovascular amyloid-β (Aβ) protein in Aβ Precursor Protein (APP) transgenic mice overexpressing vasculotropic Aβ. We investigated whether lower-dose cilostazol can decrease micro-hemorrhages and Aβ deposition in the brain using APP transgenic mice. At baseline, 14-month-old female Tg2576 mice were randomly assigned to a control group (vehicle), aspirin group (0.01% aspirin), or cilostazol group (0.01% cilostazol). The severity of cerebral micro-hemorrhages (i.e., number), area of senile plaque, and severity of vascular amyloid burden (quantified with cerebral amyloid angiopathy (CAA) score (=number of Aβ-positive vessels × severity of amyloid burden of Aβ-positive vessels) were evaluated in the brain of mice aged 15 and 21–23 months. At 15 months, no differences were shown in each pathological change among the three groups. At 21–23 months, there were no differences in the severity of cerebral micro-hemorrhages or area of senile plaque among the three groups. However, the CAA score was significantly lower in the cilostazol compared to the control group (p = 0.046, Mann–Whitney U test), although no difference was seen between the control and aspirin group. Our study showed that lower-dose cilostazol could reduce the vascular amyloid burden without increasing cerebral micro-hemorrhages in APP transgenic mice.
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spelling pubmed-71773052020-04-28 Low-Dose Phosphodiesterase III Inhibitor Reduces the Vascular Amyloid Burden in Amyloid-β Protein Precursor Transgenic Mice Yakushiji, Yusuke Kawamoto, Kazuhiro Uchihashi, Kazuyoshi Ihara, Masafumi Aoki, Shigehisa Nagaishi, Yukiko Suzuyama, Kohei Tsugitomi, Yumiko Hara, Hideo Int J Mol Sci Article A previous study reported that relatively high-dose cilostazol (0.3%) promoted the drainage of cerebrovascular amyloid-β (Aβ) protein in Aβ Precursor Protein (APP) transgenic mice overexpressing vasculotropic Aβ. We investigated whether lower-dose cilostazol can decrease micro-hemorrhages and Aβ deposition in the brain using APP transgenic mice. At baseline, 14-month-old female Tg2576 mice were randomly assigned to a control group (vehicle), aspirin group (0.01% aspirin), or cilostazol group (0.01% cilostazol). The severity of cerebral micro-hemorrhages (i.e., number), area of senile plaque, and severity of vascular amyloid burden (quantified with cerebral amyloid angiopathy (CAA) score (=number of Aβ-positive vessels × severity of amyloid burden of Aβ-positive vessels) were evaluated in the brain of mice aged 15 and 21–23 months. At 15 months, no differences were shown in each pathological change among the three groups. At 21–23 months, there were no differences in the severity of cerebral micro-hemorrhages or area of senile plaque among the three groups. However, the CAA score was significantly lower in the cilostazol compared to the control group (p = 0.046, Mann–Whitney U test), although no difference was seen between the control and aspirin group. Our study showed that lower-dose cilostazol could reduce the vascular amyloid burden without increasing cerebral micro-hemorrhages in APP transgenic mice. MDPI 2020-03-26 /pmc/articles/PMC7177305/ /pubmed/32225099 http://dx.doi.org/10.3390/ijms21072295 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yakushiji, Yusuke
Kawamoto, Kazuhiro
Uchihashi, Kazuyoshi
Ihara, Masafumi
Aoki, Shigehisa
Nagaishi, Yukiko
Suzuyama, Kohei
Tsugitomi, Yumiko
Hara, Hideo
Low-Dose Phosphodiesterase III Inhibitor Reduces the Vascular Amyloid Burden in Amyloid-β Protein Precursor Transgenic Mice
title Low-Dose Phosphodiesterase III Inhibitor Reduces the Vascular Amyloid Burden in Amyloid-β Protein Precursor Transgenic Mice
title_full Low-Dose Phosphodiesterase III Inhibitor Reduces the Vascular Amyloid Burden in Amyloid-β Protein Precursor Transgenic Mice
title_fullStr Low-Dose Phosphodiesterase III Inhibitor Reduces the Vascular Amyloid Burden in Amyloid-β Protein Precursor Transgenic Mice
title_full_unstemmed Low-Dose Phosphodiesterase III Inhibitor Reduces the Vascular Amyloid Burden in Amyloid-β Protein Precursor Transgenic Mice
title_short Low-Dose Phosphodiesterase III Inhibitor Reduces the Vascular Amyloid Burden in Amyloid-β Protein Precursor Transgenic Mice
title_sort low-dose phosphodiesterase iii inhibitor reduces the vascular amyloid burden in amyloid-β protein precursor transgenic mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177305/
https://www.ncbi.nlm.nih.gov/pubmed/32225099
http://dx.doi.org/10.3390/ijms21072295
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