Title : Tai chi-induced exosomal LRP1 is associated with memory function and hippocampal plasticity in aMCI patients
Abstract:
Aims: 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).
Methods: 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). 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. 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.
Highlights"
What is the primary question addressed by this study?
Exercise, including Tai Chi (TC) was beneficial for cognitive function of older adults with aMCI. However, the underlying molecular mechanism of TC on neuroprotection remains largely unknown. Exercise-released exosomes have been identified as novel mediators of cell-to-cell communication, playing a significant role in regulating hippocampal synaptic plasticity and nerve regeneration, as evidenced by ex vivo trials. No previous studies were done to address the gap in understanding the relationship between exercise-induced exosome, therapeutically hippocampus plasticity, and neurocognitive function response to TC training by using proteomics technology.
What is the main finding of this study?
Tai Chi exercise ameliorated cognitive function, increased right hippocampus volume, enhanced rsFC between hippocampus and cuneus which mediated the group effect on cognition and promoted circulating LRP1 release via exosome. Significant relationship was found between upregulated LRP1, memory function and hippocampus plasticity.
What is the meaning of the finding?
To our knowledge, this is the first RCT to demonstrate the potential peripheral processes of circulating exosomes in response to TC exercise and its relationship with cognitive protection and hippocampus plasticity based on large-scale proteomics analysis. Our findings provided an insight into potential therapeutic neurobiological targets for aMCI by focusing on peripheric exosome in respond to TC exercise.
