Author(s): LONGO, B., OTAVIANO, S., CAMPOS, H., FIGUEIREDO, E., PENITENTE, A., SILVA, E., SHECAIRA, T., NASCIMENTO, F.A., LOSS, C., VAN PRAAG, H., DE ANGELIS, K., ARIDA, R., Institution: UNIVERSIDADE FEDERAL DE SÃO PAULO - UNIFESP, Country: BRAZIL, Abstract-ID: 1489

INTRODUCTION:
Alzheimer’s disease (AD) is a neurodegenerative disorder and the leading cause of dementia, characterized by cognitive decline and neuronal and vascular dysfunction. AD is also recognized as a systemic condition associated with metabolic alterations, mitochondrial dysfunction, and redox imbalance in peripheral tissues including skeletal muscle. Postmenopausal women face a higher risk of AD driven by a combination of factors that may contribute to disease vulnerability and progression. Aerobic training (AT) has beneficial effects on these factors and may interfere with the progression of AD. In this study, we investigated the neuroprotective effects of AT in female APP/PS1 mice, a well stablished AD model, focusing on locomotor activity, cognition, anxiety- and depression-like behaviors, and hippocampal Aβ plaques, neuroinflammation, and vascularization. We also assessed whether AT modulates muscle oxidative stress in the gastrocnemius.
METHODS:
Six-month-old female APP/PS1 mice and wild-type (WT) controls were assigned to four groups (WT sedentary n=18; WT trained n=14; APP/PS1 sedentary n=11; APP/PS1 trained n=15). The trained groups underwent eight weeks of AT in treadmill. After the training program, locomotor activity, learning and memory, and anxiety- and depression-like behaviors were tested. Hippocampal immunohistochemistry was used to quantify Aβ plaques (6E10), microglia (Iba-1), astrocytes (GFAP), and vascular marker (tomato lectin). In the gastrocnemius, oxidative stress markers were quantified, including TBARS, protein carbonyls, hydrogen peroxide, and NADPH oxidase activity, as well as antioxidant defenses (SOD, GPx, and FRAP).
RESULTS:
AT rescued deficits in learning and memory (p<0.001), also produced anxiolytic (p<.001) and antidepressant-like effects (p<0.001) in APP/PS1 mice. In the hippocampus, AT decreased Iba-1 and GFAP immunoreactivity (p<0.001 and p=0.003 respectively). In addition, AT restored hippocampal vascularization in APP/PS1 mice to WT-like levels (p<0.001). These cognitive and tissue-level improvements occurred without a significant reduction in Aβ plaque deposition. At the peripheral level, AT improved muscle oxidative stress in APP/PS1 mice, SOD activity was reduced in sedentary groups and was restored in APP/PS1 trained to levels comparable to WT (carbonyls p<0.001 and SOD activity p=0.008), whereas other markers did not differ among groups.
CONCLUSION:
In female APP/PS1 mice, AT produced behavioral benefits, decreased neuroinflammatory markers and improved hippocampal vascularization. Moreover, AT improved muscle redox status and rescued a key antioxidant defense. Collectively, these findings indicate that aerobic exercise promotes central and peripheral resilience in female mice committed with AD.