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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN NEUROSCIENCE; v. 17, p. 11-pg., 2023-04-06.

Resumo

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)

• Processo FAPESP: 18/07366-4 - Receptores de purinas e cininas como alvos de estudo e intervenção terapêutica em doenças neurológicas
• Beneficiário: Alexander Henning Ulrich
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 22/00249-8 - Avaliação dos efeitos do exercício físico resistido e da indução da amiloidogênese e neuroinflamação em modelos in vivo e in vitro da Doença de Alzheimer
• Beneficiário: Beatriz de Oliveira Monteiro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/17504-5 - Efeitos comportamentais e moleculares da modulação farmacológica dos receptores P2Y2 em modelo animal da Doença de Alzheimer
• Beneficiário: Deidiane Elisa Ribeiro
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 21/01478-8 - Efeitos moleculares da modulação farmacológica dos receptores P2Y6 em modelo in vitro para estudo da Doença de Alzheimer
• Beneficiário: Milena da Silva Milanis
• Modalidade de apoio: Bolsas no Brasil - Mestrado