Cargando…

Nasal Rifampicin Improves Cognition in a Mouse Model of Dementia with Lewy Bodies by Reducing α-Synuclein Oligomers

α-Synuclein oligomers are thought to play an important role in the pathogenesis of dementia with Lewy bodies (DLB). There is no effective cure for DLB at present. Previously, we demonstrated that in APP- and tau-transgenic mice, oral or intranasal rifampicin reduced brain Aβ and tau oligomers and im...

Descripción completa

Detalles Bibliográficos
Autores principales: Umeda, Tomohiro, Hatanaka, Yukari, Sakai, Ayumi, Tomiyama, Takami
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395129/
https://www.ncbi.nlm.nih.gov/pubmed/34445158
http://dx.doi.org/10.3390/ijms22168453
_version_ 1783744102975668224
author Umeda, Tomohiro
Hatanaka, Yukari
Sakai, Ayumi
Tomiyama, Takami
author_facet Umeda, Tomohiro
Hatanaka, Yukari
Sakai, Ayumi
Tomiyama, Takami
author_sort Umeda, Tomohiro
collection PubMed
description α-Synuclein oligomers are thought to play an important role in the pathogenesis of dementia with Lewy bodies (DLB). There is no effective cure for DLB at present. Previously, we demonstrated that in APP- and tau-transgenic mice, oral or intranasal rifampicin reduced brain Aβ and tau oligomers and improved mouse cognition. In the present study, we expanded our research to DLB. Rifampicin was intranasally administered to 6-month-old A53T-mutant α-synuclein-transgenic mice at 0.1 mg/day for 1 month. The mice displayed memory impairment but no motor deficit at this age, indicating a suitable model of DLB. α-Synuclein pathologies were examined by the immunohistochemical/biochemical analyses of brain tissues. Cognitive function was evaluated by the Morris water maze test. Intranasal rifampicin significantly reduced the levels of [pSer129] α-synuclein in the hippocampus and α-synuclein oligomers in the visual cortex and hippocampus. The level of the presynaptic marker synaptophysin in the hippocampus was recovered to the level in non-transgenic littermates. In the Morris water maze, a significant improvement in spatial reference memory was observed in rifampicin-treated mice. Taken together with our previous findings, these results suggest that intranasal rifampicin is a promising remedy for the prevention of neurodegenerative dementia, including Alzheimer’s disease, frontotemporal dementia, and DLB.
format Online
Article
Text
id pubmed-8395129
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-83951292021-08-28 Nasal Rifampicin Improves Cognition in a Mouse Model of Dementia with Lewy Bodies by Reducing α-Synuclein Oligomers Umeda, Tomohiro Hatanaka, Yukari Sakai, Ayumi Tomiyama, Takami Int J Mol Sci Article α-Synuclein oligomers are thought to play an important role in the pathogenesis of dementia with Lewy bodies (DLB). There is no effective cure for DLB at present. Previously, we demonstrated that in APP- and tau-transgenic mice, oral or intranasal rifampicin reduced brain Aβ and tau oligomers and improved mouse cognition. In the present study, we expanded our research to DLB. Rifampicin was intranasally administered to 6-month-old A53T-mutant α-synuclein-transgenic mice at 0.1 mg/day for 1 month. The mice displayed memory impairment but no motor deficit at this age, indicating a suitable model of DLB. α-Synuclein pathologies were examined by the immunohistochemical/biochemical analyses of brain tissues. Cognitive function was evaluated by the Morris water maze test. Intranasal rifampicin significantly reduced the levels of [pSer129] α-synuclein in the hippocampus and α-synuclein oligomers in the visual cortex and hippocampus. The level of the presynaptic marker synaptophysin in the hippocampus was recovered to the level in non-transgenic littermates. In the Morris water maze, a significant improvement in spatial reference memory was observed in rifampicin-treated mice. Taken together with our previous findings, these results suggest that intranasal rifampicin is a promising remedy for the prevention of neurodegenerative dementia, including Alzheimer’s disease, frontotemporal dementia, and DLB. MDPI 2021-08-06 /pmc/articles/PMC8395129/ /pubmed/34445158 http://dx.doi.org/10.3390/ijms22168453 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Umeda, Tomohiro
Hatanaka, Yukari
Sakai, Ayumi
Tomiyama, Takami
Nasal Rifampicin Improves Cognition in a Mouse Model of Dementia with Lewy Bodies by Reducing α-Synuclein Oligomers
title Nasal Rifampicin Improves Cognition in a Mouse Model of Dementia with Lewy Bodies by Reducing α-Synuclein Oligomers
title_full Nasal Rifampicin Improves Cognition in a Mouse Model of Dementia with Lewy Bodies by Reducing α-Synuclein Oligomers
title_fullStr Nasal Rifampicin Improves Cognition in a Mouse Model of Dementia with Lewy Bodies by Reducing α-Synuclein Oligomers
title_full_unstemmed Nasal Rifampicin Improves Cognition in a Mouse Model of Dementia with Lewy Bodies by Reducing α-Synuclein Oligomers
title_short Nasal Rifampicin Improves Cognition in a Mouse Model of Dementia with Lewy Bodies by Reducing α-Synuclein Oligomers
title_sort nasal rifampicin improves cognition in a mouse model of dementia with lewy bodies by reducing α-synuclein oligomers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395129/
https://www.ncbi.nlm.nih.gov/pubmed/34445158
http://dx.doi.org/10.3390/ijms22168453
work_keys_str_mv AT umedatomohiro nasalrifampicinimprovescognitioninamousemodelofdementiawithlewybodiesbyreducingasynucleinoligomers
AT hatanakayukari nasalrifampicinimprovescognitioninamousemodelofdementiawithlewybodiesbyreducingasynucleinoligomers
AT sakaiayumi nasalrifampicinimprovescognitioninamousemodelofdementiawithlewybodiesbyreducingasynucleinoligomers
AT tomiyamatakami nasalrifampicinimprovescognitioninamousemodelofdementiawithlewybodiesbyreducingasynucleinoligomers