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

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.

Effect of Early Inhibition of Toll-Like Receptor 4 on Hippocampal Plasticity in a Neonatal Rat Model of Hypoxic-Ischemic Brain Damage.

Hippocampal plasticity is closely related to physiological brain functions such as learning and memory. However, the effect of toll-like receptor 4 (TLR4) activation on hippocampal plasticity after neonatal hypoxic-ischaemic brain damage (HIBD) remains unclear. In our study, seven-day-old rat pups were randomly categorised into three groups: control, hypoxic-ischemia (HI), and HI + TAK-242 (TAK-242). The pups were ligated in the left common carotid artery and then subjected to hypoxia to establish the neonatal HIBD model.The expression of the TLR4 in the left hippocampus of the HI group was increased compared to the control group, while TAK-242 reduced the expression level at 3 days after HIBD. Additionally, TAK-242 reversed the increased Zea-Longa score, increased the left/right hippocampal weight ratio, and increased the number of Nissl-positive neurons in the hippocampal CA1 region compared to HI group at 3 days after HIBD. Pre-injection of TAK-242 alleviated the decrease in PSD95, Aggrecan and NR1, BDNF, CREB, and pCREB expression in the hippocampus at 24 h after HIBD. It also alleviated the decrease in PSD95, BDNF, and NR2A/NR1 expression in the hippocampus at 7 days after HIBD. Furthermore, Pre-injection of TAK-242 alleviated the decrease in NR2A/NR1 expression at 21 days after HIBD. Finally,TAK-242 increased the percentage of third-grade dendritic mushroom spines processes in the basal and apical segments of neurons in the hippocampal CA1 region at 21 days after HIBD.Therefore, we conclude that preinhibition of TLR4 prior to neonatal HIBD improved the plasticity of the hippocampus.

Environmental enrichment: a systematic review on the effect of a changing spatial complexity on hippocampal neurogenesis and plasticity in rodents, with considerations for translation to urban and built environments for humans.

Introduction: Hippocampal neurogenesis is critical for improving learning, memory, and spatial navigation. Inhabiting and navigating spatial complexity is key to stimulating adult hippocampal neurogenesis (AHN) in rodents because they share similar hippocampal neuroplasticity characteristics with humans. AHN in humans has recently been found to persist until the tenth decade of life, but it declines with aging and is influenced by environmental enrichment. This systematic review investigated the impact of spatial complexity on neurogenesis and hippocampal plasticity in rodents, and discussed the translatability of these findings to human interventions. Methods: Comprehensive searches were conducted on three databases in English: PubMed, Web of Science, and Scopus. All literature published until December 2023 was screened and assessed for eligibility. A total of 32 studies with original data were included, and the process is reported in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and checklist. Results: The studies evaluated various models of spatial complexity in rodents, including environmental enrichment, changes to in-cage elements, complex layouts, and navigational mazes featuring novelty and intermittent complexity. A regression equation was formulated to synthesize key factors influencing neurogenesis, such as duration, physical activity, frequency of changes, diversity of complexity, age, living space size, and temperature. Conclusion: Findings underscore the cognitive benefits of spatial complexity interventions and inform future translational research from rodents to humans. Home-cage enrichment and models like the Hamlet complex maze and the Marlau cage offer insight into how architectural design and urban navigational complexity can impact neurogenesis in humans. In-space changing complexity, with and without physical activity, is effective for stimulating neurogenesis. While evidence on intermittent spatial complexity in humans is limited, data from the COVID-19 pandemic lockdowns provide preliminary evidence. Existing equations relating rodent and human ages may allow for the translation of enrichment protocol durations from rodents to humans.