Naz, Sabahat (2024) The role of exercise training intensity on the hippocampal proteome of middle-aged mice. Research Master thesis, Victoria University.

Abstract

It is well established that regular aerobic exercise improves memory and cognition, implicating it as a method to maintain a healthy brain throughout the lifespan. However, the ‘optimal prescription’ of aerobic exercise training, precisely training intensity, to promote these beneficial effects remains unclear. It has been hypothesised that a higher exercise training intensity may play a crucial role in augmenting the positive effects of exercise on brain health; however, the influence of exercise intensity on the brain proteome is currently unknown. The hippocampus, a critical region for memory and cognitive function, plays a key role in brain plasticity and neuroprotection. This study aims to elucidate the effects of two different exercise training intensities on the hippocampal proteome and markers of neuroprotection (e.g., pathways associated with adult neurogenesis and mitochondrial characteristics). Middle-aged mice completed 6 weeks of either moderate-intensity continuous training (MICT), high-intensity interval training (HIIT), or a passive control (CON). Hippocampal tissues were obtained at the end of the 6-week intervention and subjected to quantitative proteomic profiling using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Bioinformatic analysis was employed to analyse the biological processes and molecular pathways associated with the differentially expressed proteins. Among the 1725 identified proteins, 1143 proteins were differentially expressed across all three groups. The differential expression analysis revealed distinct expression profiles for the HIIT group compared to the MICT and CON groups, while the proteomic profiles of the MICT and CON groups were almost identical. Notably, only seven proteins were differentially expressed in the MICT vs. CON comparison, indicating a minimal impact of MICT on the hippocampal proteome. This led us to focus our subsequent analysis primarily on the HIIT vs CON comparison, where 424 proteins were significantly differentially expressed (205 upregulated and 219 downregulated). Bioinformatic analysis revealed that HIIT significantly upregulated pathways related to mRNA splicing, ribosomal RNA processing, and protein translation, implicating it as a regulator of cellular processes essential for maintaining neuronal homeostasis. In addition, we observed 77 mitochondrial proteins that were differentially expressed following HIIT, including proteins involved in the citric acid cycle, oxidative phosphorylation, and fatty acid metabolism. However, only 22 of these 77 mitochondrial proteins remained significantly different after mitochondrial normalisation, suggesting that most of the differences in mitochondrial protein expression can be attributed to training-induced changes in mitochondrial content. Taken together, these results highlight the important regulatory role of exercise training intensity on the hippocampal proteome, providing further support for studies suggesting that high-intensity exercise has more pronounced positive effects on brain health and neuroprotection.

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