Evidence map›Paper›PMID 40033045›Full record

ArticleMolecular psychiatry2025

Paranodal instability driven by axonal mitochondrial accumulation in ischemic demyelination and cognitive decline.

Yiwei Feng, Min Guo, Tongyao You, Minjie Zhang, Jincheng Li, Junchao Xie, Sida Han, Hongchen Zhao, Yanfeng Jiang, Yanxin Zhao and 3 more

Abstract read
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In one paragraph

Article in Molecular psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

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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

13 authors.

Yiwei Feng *Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
Min Guo *Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
Tongyao You *Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
Minjie ZhangDepartment of Neurology, The 10th People's Hospital, Tongji University, Shanghai, China.
Jincheng LiState Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China.
Junchao XieDepartment of Neurology, The 10th People's Hospital, Tongji University, Shanghai, China.
Sida HanDepartment of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
Hongchen ZhaoDepartment of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
Yanfeng JiangState Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China.
Yanxin ZhaoDepartment of Neurology, The 10th People's Hospital, Tongji University, Shanghai, China. zhao_yanxin@126.com.
Jintai YuDepartment of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China. jintai_yu@fudan.edu.cn.ORCID 0000-0002-2532-383X
Qiang DongDepartment of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China. dong_qiang@fudan.edu.cn.ORCID 0000-0002-3874-0130
Mei CuiDepartment of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China. cuimei@fudan.edu.cn.

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82071197National Natural Science Foundation of China (National Science Foundation of China) 82101336National Natural Science Foundation of China (National Science Foundation of China) 82271221National Natural Science Foundation of China (National Science Foundation of China) 82373658
6 · The paper itself

Abstract

backgroundSubcortical ischemic demyelination is the primary cause of vascular cognitive impairment in the elderly. However, its underlying mechanisms remain elusive.

methodsUsing a bilateral common carotid artery stenosis (BACS) mouse model and an in vitro cerebellar slice model treated with low glucose-low oxygen (LGLO), we investigated a novel mechanism of vascular demyelination.

resultsThis work identified syntaphilin-mediated docking of mitochondria as the initial event preceding ischemic demyelination. This axonal insult drives paranodal retraction, myelin instability, and subsequent cognitive impairment through excessive oxidation of protein 4.1B by mitochondrial ROS. Syntaphilin knockdown reestablished the balance of mitochondrial axoplasmic transport, reduced axonal ROS burden, and consequently decreased the abnormal oxidation of protein 4.1B, an essential component that secures the Caspr1/contactin-1/NF155 complex tethered to the axonal cytoskeleton βII-Spectrin within paranodes. This ultimately protected the paranodal structure and myelin and improved cognitive function.

conclusionsOur findings reveal a distinct pathological characteristic of ischemic demyelination and highlight the therapeutic potential of modulating axonal mitochondrial mobility to stabilize myelin structures and improve vascular cognitive impairment.

Indexed as

Cognitive DysfunctionDemyelinating DiseasesAnimalsAxonsBrain IschemiaCarotid StenosisDisease Models, AnimalMaleMembrane ProteinsMiceMice, Inbred C57BLMitochondriaMyelin SheathNerve Tissue ProteinsReactive Oxygen SpeciesMembrane ProteinsNerve Tissue ProteinsReactive Oxygen Species

Identifiers

PMID40033045

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