Neuroprotective effects of resistance physical exercise on the APP/PS1 mouse model of Alzheimer's disease

Author(s)

Campos, Henrique Correia ; Ribeiro, Deidiane Elisa ; Hashiguchi, Debora ; Glaser, Talita ; Milanis, Milena da Silva ; Gimenes, Christiane ; Suchecki, Deborah ; Arida, Ricardo Mario ; Ulrich, Henning ; Monteiro Longo, Beatriz

• Document type: Journal article
• Source: FRONTIERS IN NEUROSCIENCE; v. 17, p. 11-pg., 2023-04-06.

Abstract

IntroductionPhysical exercise has beneficial effects by providing neuroprotective and anti-inflammatory responses to AD. Most studies, however, have been conducted with aerobic exercises, and few have investigated the effects of other modalities that also show positive effects on AD, such as resistance exercise (RE). In addition to its benefits in developing muscle strength, balance and muscular endurance favoring improvements in the quality of life of the elderly, RE reduces amyloid load and local inflammation, promotes memory and cognitive improvements, and protects the cortex and hippocampus from the degeneration that occurs in AD. Similar to AD patients, double-transgenic APPswe/PS1dE9 (APP/PS1) mice exhibit Alpha beta plaques in the cortex and hippocampus, hyperlocomotion, memory deficits, and exacerbated inflammatory response. Therefore, the aim of this study was to investigate the effects of 4 weeks of RE intermittent training on the prevention and recovery from these AD-related neuropathological conditions in APP/PS1 mice. MethodsFor this purpose, 6-7-month-old male APP/PS1 transgenic mice and their littermates, negative for the mutations (CTRL), were distributed into three groups: CTRL, APP/PS1, APP/PS1+RE. RE training lasted four weeks and, at the end of the program, the animals were tested in the open field test for locomotor activity and in the object recognition test for recognition memory evaluation. The brains were collected for immunohistochemical analysis of A beta plaques and microglia, and blood was collected for plasma corticosterone by ELISA assay. ResultsAPP/PS1 transgenic sedentary mice showed increased hippocampal A beta plaques and higher plasma corticosterone levels, as well as hyperlocomotion and reduced central crossings in the open field test, compared to APP/PS1 exercised and control animals. The intermittent program of RE was able to recover the behavioral, corticosterone and A beta alterations to the CTRL levels. In addition, the RE protocol increased the number of microglial cells in the hippocampus of APP/PS1 mice. Despite these alterations, no memory impairment was observed in APP/PS1 mice in the novel object recognition test. DiscussionAltogether, the present results suggest that RE plays a role in alleviating AD symptoms, and highlight the beneficial effects of RE training as a complementary treatment for AD. (AU)

• FAPESP's process: 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 22/00249-8 - Evaluation of the effects of resistance exercise and induction of amyloidogenesis and neuroinflammation in in vivo and in vitro models of Alzheimer's Disease
• Grantee: Beatriz de Oliveira Monteiro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/17504-5 - Behavioral and molecular effects of pharmacological modulation of the P2Y2 receptors in an animal model of Alzheimer's Disease
• Grantee: Deidiane Elisa Ribeiro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 21/01478-8 - Molecular effects of pharmacological modulation of P2Y6 receptors in an in vitro model for the study of Alzheimer's Disease
• Grantee: Milena da Silva Milanis
• Support Opportunities: Scholarships in Brazil - Master