Evidence map›Paper›PMID 38790036›Full record

ArticleMolecular brain2024

A novel mouse model for investigating α-synuclein aggregates in oligodendrocytes: implications for the glial cytoplasmic inclusions in multiple system atrophy.

Tomoyuki Ishimoto, Miki Oono, Seiji Kaji, Takashi Ayaki, Katsuya Nishida, Itaru Funakawa, Takakuni Maki, Shu-Ichi Matsuzawa, Ryosuke Takahashi, Hodaka Yamakado

Abstract read
In one paragraph

Article in Molecular brain, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Tomoyuki IshimotoDepartment of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan.
Miki OonoDepartment of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan.
Seiji KajiDepartment of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan.
Takashi AyakiDepartment of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan.
Katsuya NishidaDepartment of Neurology, National Hospital Organization Hyogo-Chuo National Hospital, 1314 Ohara, Sanda, 669-1592, Japan.
Itaru FunakawaDepartment of Neurology, National Hospital Organization Hyogo-Chuo National Hospital, 1314 Ohara, Sanda, 669-1592, Japan.
Takakuni MakiDepartment of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan.
Shu-Ichi MatsuzawaDepartment of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan.
Ryosuke TakahashiDepartment of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan. ryosuket@kuhp.kyoto-u.ac.jp.
Hodaka YamakadoDepartment of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan. yamakado@kuhp.kyoto-u.ac.jp.ORCID 0000-0002-0004-2839

Funding

Japan Society for the Promotion of Science 19K16277Japan Society for the Promotion of Science 20H03590Japan Society for the Promotion of Science 21H04816Japan Society for the Promotion of Science 21K20901Moonshot Research and Development Program JPMJMS2024
6 · The paper itself

Abstract

The aggregated alpha-synuclein (αsyn) in oligodendrocytes (OLGs) is one of the pathological hallmarks in multiple system atrophy (MSA). We have previously reported that αsyn accumulates not only in neurons but also in OLGs long after the administration of αsyn preformed fibrils (PFFs) in mice. However, detailed spatial and temporal analysis of oligodendroglial αsyn aggregates was technically difficult due to the background neuronal αsyn aggregates. The aim of this study is to create a novel mouse that easily enables sensitive and specific detection of αsyn aggregates in OLGs and the comparable analysis of the cellular tropism of αsyn aggregates in MSA brains. To this end, we generated transgenic (Tg) mice expressing human αsyn-green fluorescent protein (GFP) fusion proteins in OLGs under the control of the 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNP) promoter (CNP-SNCAGFP Tg mice). Injection of αsyn PFFs in these mice induced distinct GFP-positive aggregates in the processes of OLGs as early as one month post-inoculation (mpi), and their number and size increased in a centripetal manner. Moreover, MSA-brain homogenates (BH) induced significantly more oligodendroglial αsyn aggregates than neuronal αsyn aggregates compared to DLB-BH in CNP-SNCAGFP Tg mice, suggestive of their potential tropism of αsyn seeds for OLGs. In conclusion, CNP-SNCAGFP Tg mice are useful for studying the development and tropism of αsyn aggregates in OLGs and could contribute to the development of therapeutics targeting αsyn aggregates in OLGs.

Indexed as

alpha-SynucleinInclusion BodiesMultiple System AtrophyOligodendrogliaProtein AggregatesAnimalsBrainCytoplasmDisease Models, AnimalGreen Fluorescent ProteinsHumansMiceMice, TransgenicProtein Aggregation, Pathologicalalpha-SynucleinGreen Fluorescent ProteinsProtein AggregatesCellular tropismGCIGlial cytoplasmic inclusionsMouse modelMSAMultiple system atrophyPrion hypothesisPropagationα-synuclein

Identifiers

PMID38790036
PMCPMC11127389

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.