Treadmill Exercise Ameliorates Adult Hippocampal Neurogenesis Possibly by Adjusting the APP Proteolytic Pathway in APP/PS1 Transgenic Mice

• Published in: International journal of molecular sciences Vol. 22; no. 17; p. 9570
• Main Authors: Yu, Haizhen, Zhang, Chenfei, Xia, Jie, Xu, Bo
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.09.2021; MDPI
• Subjects: Aerobics; Alzheimer's disease; Amyloid precursor protein; Amyloidogenesis; Animal models; Apoptosis; APP proteolytic pathway; Behavior; Cell differentiation; Cell proliferation; Cognition & reasoning; Exercise; Fitness equipment; Genotype & phenotype; hippocampal microenvironment; hippocampal neurogenesis; Hippocampus; Learning; Localization; Memory; Microenvironments; Molecular modelling; Neurogenesis; Neurotrophic factors; Physical exercise; Physical fitness; Presenilin 1; Proteolysis; Rodents; Transgenic animals; Transgenic mice; treadmill exercise; Treadmills
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22179570

Alzheimer’s disease (AD) is a neurodegenerative disorder known to cause cognitive impairment among the elderly worldwide. Although physical exercise-induced adult hippocampal neurogenesis (AHN) improves cognition, understanding its underlying molecular mechanisms requires further investigation using AD mouse models. In this present work, we subjected amyloid precursor protein (APP)/PS1 mice to a 12-week aerobic treadmill exercise to investigate AHN and its potential mechanisms. We divided 3-month-old littermates wild-type and APP/PS1 transgenic male mice into four groups, and the exercise groups performed 12-week treadmill exercise. Next, we evaluated the influence of treadmill exercise on learning and memory capacity, AHN, and APP proteolytic pathway-related factors. As per our results, the treadmill exercise was able to improve the hippocampal microenvironment in APP/PS1 mice probably by regulating various neurotrophic factors and secretases resulting in APP cleavage through a non-amyloidogenic pathway, which seems to further promote new cell proliferation, survival, and differentiation, enhancing hippocampal neurogenesis. All of these effects ameliorate learning and memory capacity. This study provides a theoretical and experimental basis for understanding AHN in an AD mouse model, which is beneficial for preventing and treating AD.