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细胞外囊泡有助于运动训练对APP/PS1小鼠产生有益影响。

Extracellular vesicles contribute to the beneficial effects of exercise training in APP/PS1 mice.

作者信息

Fuller Oliver K, McLennan Emma D, Egan Casey L, Perera Nimna, Terry Lauren V, Pyun Jae, de Mendonca Mariana, Telles Guilherme Defante, Smeuninx Benoit, Burrows Emma L, Siddiqui Ghizal, Creek Darren J, Scott John W, Pearen Michael A, Fonseka Pamali, Nicolazzo Joseph A, Mathivanan Suresh, Hannan Anthony J, Ramm Grant A, Whitham Martin, Febbraio Mark A

机构信息

Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia.

Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.

出版信息

iScience. 2025 Jan 4;28(2):111752. doi: 10.1016/j.isci.2025.111752. eCollection 2025 Feb 21.

DOI:10.1016/j.isci.2025.111752
PMID:39898049
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11787611/
Abstract

Exercise improves cognitive function in Alzheimer's disease (AD) via mechanism that are not fully clear. Here, we first examined the effect of voluntary exercise training (VET) on energy metabolism and cognitive function in the APP/PS1 transgenic mouse (Tg) model of familial AD. Next, we profiled extracellular vesicles (EVs) and examined whether they may play a role in the protective effects of VET via intranasal administration of EVs, purified from the blood of sedentary (sEV) and/or acutely exercised (eEV) donor wild-type mice into APP/PS1Tg mice. We show that VET reduced resting energy expenditure (REE) and improved cognition in APP/PS1 Tg mice. Administration of eEV, but not sEV, also reduced REE, but had no effect on cognition. Taken together, these data show that exercise is effective intervention to improve symptoms of AD in APP/PS1Tg mice. In addition, eEVs mediate some of these effects, implicating EVs in the treatment of age-related neurodegenerative diseases.

摘要

运动通过尚未完全明确的机制改善阿尔茨海默病（AD）的认知功能。在此，我们首先研究了自愿运动训练（VET）对家族性AD的APP/PS1转基因小鼠（Tg）模型能量代谢和认知功能的影响。接下来，我们对细胞外囊泡（EVs）进行了分析，并通过将从久坐不动（sEV）和/或急性运动（eEV）的供体野生型小鼠血液中纯化的EVs经鼻内给药至APP/PS1 Tg小鼠，研究它们是否可能在VET的保护作用中发挥作用。我们发现VET降低了APP/PS1 Tg小鼠的静息能量消耗（REE）并改善了认知。给予eEV而非sEV也降低了REE，但对认知没有影响。综上所述，这些数据表明运动是改善APP/PS1 Tg小鼠AD症状的有效干预措施。此外，eEV介导了其中一些作用，提示EVs可用于治疗与年龄相关的神经退行性疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea65/11787611/d93d364b39f3/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea65/11787611/048d40430eaf/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea65/11787611/c372f3806ff1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea65/11787611/792c7f9a0cb0/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea65/11787611/d2afb92ecb66/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea65/11787611/77c8895f7350/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea65/11787611/b18c9efe5c7e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea65/11787611/3592a2638b30/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea65/11787611/d93d364b39f3/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea65/11787611/048d40430eaf/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea65/11787611/c372f3806ff1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea65/11787611/792c7f9a0cb0/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea65/11787611/d2afb92ecb66/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea65/11787611/77c8895f7350/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea65/11787611/b18c9efe5c7e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea65/11787611/3592a2638b30/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea65/11787611/d93d364b39f3/gr7.jpg

相似文献

[1]
Extracellular vesicles contribute to the beneficial effects of exercise training in APP/PS1 mice.

iScience. 2025-1-4

[2]
Long-term running exercise improves cognitive function and promotes microglial glucose metabolism and morphological plasticity in the hippocampus of APP/PS1 mice.

J Neuroinflammation. 2022-2-5

[3]
Enrichment of Neurodegenerative Microglia Signature in Brain-Derived Extracellular Vesicles Isolated from Alzheimer's Disease Mouse Models.

J Proteome Res. 2021-3-5

[4]
Neuroprotective effects of resistance physical exercise on the APP/PS1 mouse model of Alzheimer's disease.

Front Neurosci. 2023-4-6

[5]
Alzheimer's disease brain-derived extracellular vesicles reveal altered synapse-related proteome and induce cognitive impairment in mice.

Alzheimers Dement. 2023-12

[6]
Long-term treadmill exercise inhibits the progression of Alzheimer's disease-like neuropathology in the hippocampus of APP/PS1 transgenic mice.

Behav Brain Res. 2013-11-1

[7]
AVP(4-8) Improves Cognitive Behaviors and Hippocampal Synaptic Plasticity in the APP/PS1 Mouse Model of Alzheimer's Disease.

Neurosci Bull. 2019-10-12

[8]
Metagenome Analysis of Bodily Microbiota in a Mouse Model of Alzheimer Disease Using Bacteria-derived Membrane Vesicles in Blood.

Exp Neurobiol. 2017-12

[9]
Glucose tolerance and insulin sensitivity are impaired in APP/PS1 transgenic mice prior to amyloid plaque pathogenesis and cognitive decline.

Exp Gerontol. 2017-2

[10]
Human gut microbiota Agathobaculum butyriciproducens improves cognitive impairment in LPS-induced and APP/PS1 mouse models of Alzheimer's disease.

Nutr Res. 2021-2

引用本文的文献

[1]
The Multifaceted Role of Extracellular Vesicles in Alzheimer's Disease.

J Neurochem. 2025-8

[2]
Extracellular Vesicles for the Treatment of Alzheimer's Disease: A Systematic Review.

J Extracell Biol. 2025-8-20

本文引用的文献

[1]
Exercise training improves long-term memory in obese mice.

Life Metab. 2023-11-15

[2]
Decorin, an exercise-induced secretory protein, is associated with improved prognosis in breast cancer patients but does not mediate anti-tumorigenic tissue crosstalk in mice.

J Sport Health Sci. 2024-9-26

[3]
Exercise suppresses neuroinflammation for alleviating Alzheimer's disease.

J Neuroinflammation. 2023-3-19

[4]
Single vesicle analysis reveals the release of tetraspanin positive extracellular vesicles into circulation with high intensity intermittent exercise.

J Physiol. 2023-11

[5]
Activation of MAP2K signaling by genetic engineering or HF-rTMS promotes corticospinal axon sprouting and functional regeneration.

Sci Transl Med. 2023-1-4

[6]
Microglia Regulate Blood-Brain Barrier Integrity via MiR-126a-5p/MMP9 Axis during Inflammatory Demyelination.

Adv Sci (Weinh). 2022-8

[7]
Structural progression of Alzheimer's disease over decades: the MRI staging scheme.

Brain Commun. 2022-4-28

[8]
Exerkines in health, resilience and disease.

Nat Rev Endocrinol. 2022-5

[9]
A new mass spectral library for high-coverage and reproducible analysis of the Plasmodium falciparum-infected red blood cell proteome.

Gigascience. 2022-3-7

[10]
A Systematic Review of the Impact of Physical Exercise-Induced Increased Resting Cerebral Blood Flow on Cognitive Functions.

Front Aging Neurosci. 2022-2-14

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