Tai Chi-Induced Exosomal LRP1 is Associated With Memory Function and Hippocampus Plasticity in aMCI Patients

IF 4.4 2区 医学 Q1 GERIATRICS & GERONTOLOGY American Journal of Geriatric Psychiatry Pub Date : 2024-04-26 DOI:10.1016/j.jagp.2024.04.012
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Abstract

Objectives

The study was designed to identify the potential peripheral processes of circulating exosome in response to Tai Chi (TC) exercise and the possibility of its loaded cargos in mediating the effects of TC training on cognitive function among older adults with amnestic mild cognitive impairment (aMCI).

Design, setting, and participants

This was a multicenter randomized controlled trial. One hundred community-dwelling old adults with aMCI were randomly assigned (1:1) to experimental (n = 50) and control groups (n = 50).

Intervention

The experimental group participated in TC exercise 5 times/week, with each session lasting 60 minutes for 12 weeks. Both experimental and control groups received health education every 4 weeks.

Measurements

The primary outcome was global cognitive function. Neurocognitive assessments, MRI examination, and large-scale proteomics analysis of peripheric exosome were conducted at baseline and after 12-week training. Outcome assessors and statisticians were blinded to group allocation.

Results

A total of 96 participants (96%) completed all outcome measurements. TC training improved global cognitive function (adjusted mean difference [MD] = 1.9, 95%CI 0.93–2.87, p <0.001) and memory (adjusted MD = 6.42, 95%CI 2.09–10.74, p = 0.004), increased right hippocampus volume (adjusted MD = 88.52, 95%CI 13.63–163.4, p = 0.021), and enhanced rest state functional connectivity (rsFC) between hippocampus and cuneus, which mediated the group effect on global cognitive function (bootstrapping CIs: [0.0208, 1.2826], [0.0689, 1.2211]) and verbal delay recall (bootstrapping CI: [0.0002, 0.6277]). Simultaneously, 24 differentially expressed exosomal proteins were detected in tandem mass tag-labelling proteomic analysis. Of which, the candidate protein low-density lipoprotein receptor-related protein 1 (LRP1) was further confirmed by parallel reaction monitoring and ELISA. Moreover, the up-regulated LRP1 was both positively associated with verbal delay recall and rsFC (left hippocampus-right cuneus).

Conclusion

TC promotes LRP1 release via exosome, which was associated with enhanced memory function and hippocampus plasticity in aMCI patients. Our findings provided an insight into potential therapeutic neurobiological targets focusing on peripheric exosome in respond to TC exercise.

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太极拳诱导的外泌体 LRP1 与 aMCI 患者的记忆功能和海马区可塑性有关
该研究旨在确定循环外泌体对TC运动的潜在外周反应过程,以及其所携带的载体是否可能介导TC训练对患有失忆性轻度认知障碍(aMCI)的老年人认知功能的影响。这是一项多中心随机对照试验。100 名居住在社区、患有轻度认知障碍的老年人被随机分配(1:1)到实验组(n = 50)和对照组(n = 50)。实验组参加 TC 运动,每周 5 次,每次 60 分钟,持续 12 周。实验组和对照组每 4 周接受一次健康教育。主要结果是总体认知功能。在基线和为期12周的训练后进行了神经认知评估、核磁共振成像检查和外周外泌体的大规模蛋白质组学分析。结果评估人员和统计人员对组别分配实行盲法。共有 96 名参与者(96%)完成了所有结果测量。TC 训练改善了整体认知功能(调整后平均差 [MD] = 1.9,95%CI 0.93-2.87,p <0.001)和记忆(调整后平均差 = 6.42,95%CI 2.09-10.74,p = 0.004),增加了右侧海马体积(调整后平均差 = 90.39,95%CI 20.09-160.69,p = 0.012),并增强了静息状态。这在整体认知功能(bootstrapping CIs:[0.0208, 1.2826],[0.0689, 1.2211])和言语延迟回忆(bootstrapping CI:[0.0002, 0.6277])的群体效应中起中介作用。同时,串联质量标签标记蛋白质组学分析检测到了 24 种差异表达的外泌体蛋白质。其中,候选蛋白低密度脂蛋白受体相关蛋白 1(LRP1)通过平行反应监测和酶联免疫吸附试验得到进一步证实。此外,上调的 LRP1 与言语延迟回忆和 rsFC(左海马-右楔状体)均呈正相关。TC通过外泌体促进LRP1的释放,这与aMCI患者记忆功能和海马可塑性的增强有关。我们的研究结果提供了针对外周外泌体对TC运动反应的潜在治疗神经生物学靶点的见解。
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来源期刊
CiteScore
13.00
自引率
4.20%
发文量
381
审稿时长
26 days
期刊介绍: The American Journal of Geriatric Psychiatry is the leading source of information in the rapidly evolving field of geriatric psychiatry. This esteemed journal features peer-reviewed articles covering topics such as the diagnosis and classification of psychiatric disorders in older adults, epidemiological and biological correlates of mental health in the elderly, and psychopharmacology and other somatic treatments. Published twelve times a year, the journal serves as an authoritative resource for professionals in the field.
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Editorial Board Table of Contents In This Issue Information for Subscribers Suicidal Behavior in Older Adults With Cognitive Impairment.
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