Evaluation of the effects of resistance exercise and induction of amyloidogenesis and neuroinflammation in in vivo and in vitro models of Alzheimer's Disease

• Grant number: 22/00249-8
• Support Opportunities: Regular Research Grants
• Duration: February 01, 2023 - January 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Beatriz de Oliveira Monteiro
• Grantee: Beatriz de Oliveira Monteiro
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Alzheimer's Disease (AD) is characterized by progressive learning and memory loss, behavioral dysfunction, and changes in social interactions. The extensive deposition of the amyloid-² peptide (A²) in the form of senile plaques in the cortex and hippocampus and the presence of neurofibrillary tangles are the two main pathophysiological features of AD. In addition, AD is strongly associated with inflammatory processes involving microglial activation resulting in neurotoxicity. Recent studies have suggested the physical exercise as an effective strategy of improving memory, learning and cognitive functions in the elderly, as well as in reducing the risk of developing AD, against both clinical symptoms and also the pathophysiological markers of AD, producing anti-inflammatory and neuroprotective effects, as well as increasing neurotrophic factors and vascularization. Thus, we propose to investigate whether the intervention by different protocols of physical exercise could trigger a prolonged and sustained immunomodulatory and anti-inflammatory responses throughout the development of AD, and thus minimize cognitive impairment and neuropathological alterations related to neurodegeneration and amyloidogenesis. The role of microglia if favorable or unfavorable in view of a gradual increase in amyloidogenesis and inflammation will also be investigated, as well as the pathophysiological differences of AD between males and females under the action of physical activity, allowing comparison between the sexes regarding inflammatory response and differences in cognitive dysfunction at different times of AD development and response to physical exercise. Thus, pathophysiological and behavioral responses along the disease progression will be investigated in vivo in APP/PS1 double-transgenic mice for AD submitted to physical exercise, also taking into account the comparison between males and females. And the in vitro step will allow us to investigate the participation in A² toxicity and in the degenerative processes present in AD, related to amyloidogenesis and neuroinflammation, aiming for a better understanding of the inflammatory response and participation of glial cells in AD and for regenerative possibilities provided by physical exercise. (AU)