Exercise effects on brain and behavior in healthy mice, Alzheimer's disease and Parkinson's disease model-A systematic review and meta-analysis

This systematic review and meta-analysis examines how exercise modifies brain and behavior in healthy mice, dementia (D) and Parkinson disease (PD) models. A search was performed on the Medline and Scopus electronic databases (2008-2019). Search terms were mice, brain, treadmill, exercise, physical exercise. In the total, 430 were found but only 103 were included. Animals n = 1,172; exercised 4-8 weeks (Range 24 h to 32 weeks), 60 min/day (Range 8-120 min per day), and 10/12 m/min (Range 0.2 m/min to 36 m/min). Hippocampus, cerebral cortex, striatum and whole brain were more frequently investigated. Exercise improved learning and memory. Meta-analysis showed that exercise increased: cerebral BDNF in health (n = 150; z = 5.8, CI 3.43-12.05; p < 0.001 I2 = 94.3 %), D (n = 124; z = 4.18, CI = 2.22-9.12; p < 0.001; I2 = 93.7 %) and PD (n = 16 z = 4.26, CI 5.03-48.73 p < 0.001 I2 = 94.8 %). TrkB improved in health (n = 84 z = 5.49, CI 3.8-17.73 p < 0.001, I2 = 0.000) and PD (n = 22; z = 3.1, CI = 2.58-67.3, p < 0.002 I2 = 93.8 %). Neurogenesis increased in health (n = 68; z = 7.08, CI 5.65-21.25 p < 0.001; I2 17.58) and D model (n = 116; z = 4.18, CI 2.22-9.12 p < 0.001 I2 93.7 %). Exercise augmented amyloid clearance (n = 166; z = 7.51 CI = 4.86-14.85, p < 0.001 I2 = 58.72) and reduced amyloid plaques in D models (n = 49; z = 4.65, CI = 3.94-15.3 p < 0.001 I2 = 0.000). In conclusion, exercise improved brain and behavior, neurogenesis in healthy and dementia models, reduced toxicity and cerebral amyloid. Evidence regarding inflammation, oxidative stress and energy metabolism were scarce. Studies examining acute vs chronic exercise, extreme training and the durability of exercise benefit were rare. Vascular or glucose metabolism changes were seldom reported.