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Study of tau pathology in male rTg4510 mice fed with a curcumin derivative Shiga-Y5

Intracellular inclusions of aggregated tau appear in neurons and glial cells in a range of neurodegenerative diseases known as tauopathies. Inhibition of pathological changes in tau is a therapeutic target for tauopathy. We recently synthesized a novel curcumin derivative, named Shiga-Y5, and showed...

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Autores principales: Yanagisawa, Daijiro, Hamezah, Hamizah Shahirah, Durani, Lina Wati, Taguchi, Hiroyasu, Tooyama, Ikuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283544/
https://www.ncbi.nlm.nih.gov/pubmed/30521594
http://dx.doi.org/10.1371/journal.pone.0208440
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author Yanagisawa, Daijiro
Hamezah, Hamizah Shahirah
Durani, Lina Wati
Taguchi, Hiroyasu
Tooyama, Ikuo
author_facet Yanagisawa, Daijiro
Hamezah, Hamizah Shahirah
Durani, Lina Wati
Taguchi, Hiroyasu
Tooyama, Ikuo
author_sort Yanagisawa, Daijiro
collection PubMed
description Intracellular inclusions of aggregated tau appear in neurons and glial cells in a range of neurodegenerative diseases known as tauopathies. Inhibition of pathological changes in tau is a therapeutic target for tauopathy. We recently synthesized a novel curcumin derivative, named Shiga-Y5, and showed that Shiga-Y5 inhibited cognitive impairment and amyloid deposition in a mouse model of Alzheimer’s disease. Here we investigated whether Shiga-Y5 inhibited cognitive impairment and tau accumulation in a mouse model of tauopathy, rTg4510. The rTg4510 mouse is a bitransgenic mouse model that uses a system of responder and activator transgenes to express human four-repeat tau with the P301L mutation. This strain is obtained by crossing tetO-MAPT*P301L mouse line (on a FVB/NJ background) with CaMKII-tTA mouse line (on a C57BL/6J background). Male rTg4510 mice and wild-type mice were fed with a standard chow diet with or without Shiga-Y5 (500 ppm) for 4 months. Behavioral tests were conducted from 5.5 months of age, and the mice were sacrificed at 6 months of age. There were no significant changes in behavioral performance in rTg4510 mice fed with SY5-containing chow diet compared with rTg4510 mice fed with control chow diet. Histological and biochemical analyses also showed no significant alterations in tau accumulation by the treatment with SY5. One of noticeable finding in this study was that rTg4510 mice on a F1 female FVB/NJ x male C57BL/6J background showed more severe tau accumulation than rTg4510 mice on a F1 female C57BL/6J x male FVB/NJ background. Further studies to clarify the mechanisms underlying tau aggregation may help to develop therapeutic approaches aimed at preventing this pathological feature.
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spelling pubmed-62835442018-12-20 Study of tau pathology in male rTg4510 mice fed with a curcumin derivative Shiga-Y5 Yanagisawa, Daijiro Hamezah, Hamizah Shahirah Durani, Lina Wati Taguchi, Hiroyasu Tooyama, Ikuo PLoS One Research Article Intracellular inclusions of aggregated tau appear in neurons and glial cells in a range of neurodegenerative diseases known as tauopathies. Inhibition of pathological changes in tau is a therapeutic target for tauopathy. We recently synthesized a novel curcumin derivative, named Shiga-Y5, and showed that Shiga-Y5 inhibited cognitive impairment and amyloid deposition in a mouse model of Alzheimer’s disease. Here we investigated whether Shiga-Y5 inhibited cognitive impairment and tau accumulation in a mouse model of tauopathy, rTg4510. The rTg4510 mouse is a bitransgenic mouse model that uses a system of responder and activator transgenes to express human four-repeat tau with the P301L mutation. This strain is obtained by crossing tetO-MAPT*P301L mouse line (on a FVB/NJ background) with CaMKII-tTA mouse line (on a C57BL/6J background). Male rTg4510 mice and wild-type mice were fed with a standard chow diet with or without Shiga-Y5 (500 ppm) for 4 months. Behavioral tests were conducted from 5.5 months of age, and the mice were sacrificed at 6 months of age. There were no significant changes in behavioral performance in rTg4510 mice fed with SY5-containing chow diet compared with rTg4510 mice fed with control chow diet. Histological and biochemical analyses also showed no significant alterations in tau accumulation by the treatment with SY5. One of noticeable finding in this study was that rTg4510 mice on a F1 female FVB/NJ x male C57BL/6J background showed more severe tau accumulation than rTg4510 mice on a F1 female C57BL/6J x male FVB/NJ background. Further studies to clarify the mechanisms underlying tau aggregation may help to develop therapeutic approaches aimed at preventing this pathological feature. Public Library of Science 2018-12-06 /pmc/articles/PMC6283544/ /pubmed/30521594 http://dx.doi.org/10.1371/journal.pone.0208440 Text en © 2018 Yanagisawa et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Yanagisawa, Daijiro
Hamezah, Hamizah Shahirah
Durani, Lina Wati
Taguchi, Hiroyasu
Tooyama, Ikuo
Study of tau pathology in male rTg4510 mice fed with a curcumin derivative Shiga-Y5
title Study of tau pathology in male rTg4510 mice fed with a curcumin derivative Shiga-Y5
title_full Study of tau pathology in male rTg4510 mice fed with a curcumin derivative Shiga-Y5
title_fullStr Study of tau pathology in male rTg4510 mice fed with a curcumin derivative Shiga-Y5
title_full_unstemmed Study of tau pathology in male rTg4510 mice fed with a curcumin derivative Shiga-Y5
title_short Study of tau pathology in male rTg4510 mice fed with a curcumin derivative Shiga-Y5
title_sort study of tau pathology in male rtg4510 mice fed with a curcumin derivative shiga-y5
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283544/
https://www.ncbi.nlm.nih.gov/pubmed/30521594
http://dx.doi.org/10.1371/journal.pone.0208440
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