Mass Spectrometry Chromatography-Based Metabolomics: The Effect of Long-Term Aerobic Exercise on Learning Ability and the Metabolism of Intestinal Contents in Mice with Alzheimer's Disease.

This study aimed to investigate the effect of long-term aerobic exercise on the metabolism of intestinal contents in APP/PS1 mice was studied using a non-targeted metabolomics technique based on high-performance liquid chromatography-mass spectrometry (HPLC-MS) coupling, providing a theoretical basis for exercise to regulate the metabolism of Alzheimer's disease (AD) organisms. Three-month-old male C57BL/6JNju mice, six wild-type (NC, n = 6); 12 APP/PS1 double transgenic species in total, were randomly divided into AD model (AM, n = 6) and AD model exercise (AE, n = 6) groups. The mice in the NC group were fed naturally, the mice in the AM group were statically placed on a running platform, and the mice in the AE group received a 20-week long-term moderate intensity running platform exercise intervention. Following the exercise intervention, the cecum contents of the mice in each group were collected and analyzed using the HPLC-MS technique, with those meeting both variable important in projection (VIP)> 1.5 and p < 0.05 being screened as differential metabolites. A total of 32 different metabolites were detected between the AM and NC groups, with 19 up-regulated in the AM group such as phosphatidic acid (PA) (18:4(6Z,9Z,12Z,15Z)/21:0) and 13 down-regulated in the AM group, such as 4,8-dimethylnonanoyl, compared to the NC group; 98 different metabolites were found between the AM and AE groups, 41 of which were upregulated such as Lyso phosphatidylcholine (LysoPC) and 57 of which were downregulated compared to the AM group such as Phosphatidylinositol (PI). The regulation of linoleic acid metabolism, glycerophospholipid metabolism, bile secretion, phenylalanine metabolism, and other pathways was predominantly regulated by nine metabolites, which were subsequently identified as indicators of exercise intervention to enhance metabolism in AD mice. The metabolomic technique can identify the metabolic problems of intestinal contents in AD mice and initially screen the biomarkers of exercise to improve the metabolic disorders in AD. These findings can help us better understand the impact of aerobic exercise on AD metabolism.

Long-term exercise training inhibits inflammation by suppressing hippocampal NLRP3 in APP/PS1 mice.

Behavioral experiments have demonstrated that long-term physical exercise can be beneficial for learning and memory dysfunction caused by neuroinflammation in Alzheimer's disease (AD). However, the molecular mechanism remains poorly understood due to a lack of sufficient pertinent biochemical evidence. We investigated the potential effect of long-term physical exercise on cognition and hippocampal gene and protein expression changes in a transgenic AD mouse model. Following twenty weeks of treadmill exercise, transgenic AD mice showed improvement in cognitive functions and downregulation of Nod-like receptor protein 3 (NLRP3) (p â€‹< â€‹0.01), interleukin-1beta (IL-1ß) (p â€‹< â€‹0.05), and amyloid-ß1-42 (Aß1-42) (p â€‹< â€‹0.05) expression levels. In addition, we observed significant reductions of microglial activation and hippocampal neuronal damage in the exercised AD mice (p â€‹< â€‹0.01), which might be a result of the downregulation of NLRP3-mediated signaling and neuro-inflammatory responses. As neuronal damage due to inflammation might be a likely cause of AD-associated cognitive dysfunction. Our results suggested that the anti-inflammatory effects of exercise training involved downregulating the expression of key inflammatory factors and might play an important role in protecting hippocampal neurons against damage during the course of AD.