Table 1 The effects of exercise on neuroinflammation in AD patients or animal models
From: Exercise mimetics: a novel strategy to combat neuroinflammation and Alzheimer’s disease
Experimental models/patients | Exercise interventions | Tissues/samples | Intervention effects on inflammatory cytokines | Other outcomes | Studies |
|---|---|---|---|---|---|
Experimental animal models of AD | |||||
Male 3xTg mice, age: 3 months | 5 times of 1-h treadmill running per week, 12 weeks | Prefrontal cortex | Reduction of IL-1β, IL-6, and TNFα | i. Decrease of Aβ40 ii. Reduction of microglial and astrocyte activation | Mu et al., 2022 [411] |
Male APP/PS1 mice, age: 3 months | 5 times of 45-min treadmill running per week, 12 weeks | Hippocampus | Decrease of TNF-α and IL-1β; elevation of IL-10 and TGF-β | i. Enhancement of cognition ii. Elevation of M2 pattern microglia iii. Increase in SOD and reduction of MAD | Zhang et al., 2019 [190] |
AD mice, age: 8 weeks | Daily 30 min of treadmill exercise, 1 week | Hippocampus | Reduction of TNF-α and IL-1β | i. Decrease of Aβ ii. Reduction of reactive astrocytes iii. Increase in hippocampal neurogenesis and cognition | Sun et al., 2018 [196] |
Male AD rats | 5 times of 20 min of treadmill running per week, 4 weeks | Hippocampus | Decrease of TNF-α and IL-1β; elevation of IL-10 and IL-4 | i. Decrease of Aβ and p-tau ii. Increment of M2 phenotype microglia iii. Better novel object recognition | Lu et al., 2017 [412] |
Male Swiss mice (intracerebroventricular injection with Aβ1 − 40), age: 45–55 days | 5 times of 40 min of treadmill exercise per week, 4 weeks | Hippocampus | Reduction of IL-1β, NLRP3 and Caspase-1 | Decrease of the number of Iba-1+ microglial cells | Rosa et al., 2021 [193] |
Tg-NSE/htau23 mice, age: 16 months | 5 times weekly of 60-min treadmill exercise, 12 weeks | Hippocampus | Reduction of TNF-α, IL-6, IL-1β, COX-2, and NK-κB | Decrease of GFAP+ and MAC-1+ glial cells | Leem et al., 2011 [413] |
AD mice, age: 17 months | 3 weeks of voluntary wheel exercise | Blood | Increase in markers of alternative pathway of the complement system including clusterin, FH and C1INH | Increase in hippocampal neurogenesis and memory function | De Miguel et al., 2021 [21] |
Male and female BALB/C mice, age: 4 and 22 months | 10 weeks of voluntary wheel exercise | Hippocampus | Reduction of the number of CD86+ and MHCII+ microglia in female mice; decrease of the number of CD86+ microglia but increased MHCII+ microglia in male mice | NA | Kohman et al., 2013 [414] |
Tg2576 mice, age: 17–18 months | 3 weeks of voluntary wheel running | Hippocampus cortex | Reduction of IL-1β and TNF-α; increase in IFN-γ, MIP-1α, MHCII, and CD40 | Decrease of Aβ40 and soluble Aβ | Nichol et al., 2008 [415] |
Female 5xFAD mice, age: 2–3 months | 24 weeks of voluntary wheel running | Blood Hippocampus | Unchanged TNF-α, IL-1β, IL-4, and IL-10 | i. Unaltered cognitive function ii. Increase in anxious behavior | Svensson et al., 2020 [416] |
Female rats with AD, age: 6–12 months | 7 times weekly of 30-min swimming exercise, 4 weeks | Blood | Elevation of IL-10 and reduction of IL-6 | i. Improvement of Aβ and tau ii. Increment of BDNF, GSH, and NGF iii. Cognitive enhancement | Medhat et al., 2020 [417] |
Male SD rats with AD, age: 2.5 months | Daily 60-min swimming exercise, 4 weeks | Hippocampus | Decrease of TNF-α, IL-1β, IL-6 and IL-18 and increase in IL-10 | i. Decrease of Aβ and tau ii. Restoration of learning and memory function | Wu et al., 2018 [310] |
Male 3xTg mice, age: 9 months old | 3 times weekly of resistance training, 4 weeks | Blood liver frontal cortex hippocampus | Reduction of TNF-α and IL-1β; elevation of IL-10 | i. Decrease of Aβ and p-tau ii. Reduction of activation of glia iii. Improvement of memory function | Liu et al., 2020 [418] |
Male APP/PS1 mice, age: 6–7 months | 5 times weekly of resistance exercise, 4 weeks | Hippocampus | Reduction of IL-1α, IL-4, and IL-6 | Decease of Aβ plaques | Hashiguchi et al., 2020 [419] |
Human studies | |||||
Female AD patients, n = 15, aged 68.3 years | Physical and function training, 2 times weekly of 60-min training, 11 weeks | Blood | Increased levels of IL-4; unchanged IL-10 and TNF-α levels | i. Improvement of cognitive function, spatial judgment and self-awareness ii. Reduction of ROS | de Farias et al., 2021 [420] |
AD patients, n = 198, aged 71.4–69.9 years | Aerobic exercise, 3 times weekly of 60-min training,16 weeks | Blood CSF | Increase in plasma IL-6 and sTREM2 in CSF | NA | Jensen et al., 2019 [186] |
AD patients, n = 40, aged 68.9–69.1 years | Treadmill aerobic exercise, 3 times weekly of 45 min of intervention, 8 weeks | Blood | Reduction of plasma TNF-α and IL-6 levels | Improvement of Quality of life | Abd El-Kader and Al-Jiffri, 2016 [421] |
MCI patients, n = 50, aged 65.7 years | Aerobic exercise, 3 times of 40 min of intervention per week,16 weeks | Blood | Reduction of IL-15 and TNF-α | i. Improvement of cognitive function ii. Elevation of BNDF | Tsai et al., 2019 [422] |