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Table 1 Effects of physical exercise on brain metabolism in animal models

From: Brain metabolism in Alzheimer’s disease: biological mechanisms of exercise

Model/sex/age

Groups

Exercise protocol

Main effects of glucose/lipid/Aβ/iron/tau metabolism in the brain

Reference

Wistar rats/Male/

8 weeks

Control groups: intact control group, Aβ injected group, sham injected group

Intervention groups: exercise group, Aβ + exercise group

4-week chronic treadmill running/5 days a week/exercise intensity not indicated

NEP, IDE and LRP-1 protein levels were elevated; Aβ levels were reduced

[19]

APP-C105 mice/male/24 months

Control groups: NTg-C group, Tg-C group

Intervention groups: NTg-TE group, Tg-TE group

8-week chronic treadmill exercise/5 days a week/70%–85% VO2max

Decreased expression of Tf, TfR1, DMT1, ferritin and BACE1; increased expression of Fpn1, Furin and ADAM10; reduced iron overload

[20]

Sprague-Dawley rats/male/10 weeks

Control group: sedentary control group

Intervention group: acute exercise group

2-h single acute treadmill exercise/50%–70% VO2max/moderate intensity

Increased levels of lactate, β-hydroxybutyrate, MCT1, MCT2, MCT4 and GLUT1 proteins

[40]

APPswe/PS1∆E9 mice/male/6 months

Control groups: WT-NT, AD-NT

Intervention groups: WT-T, AD-T

4-week regular swim training/1 h each day, 6 days a week/exercise intensity not indicated

Increased expression of GLUT1 and GLUT3; reduced expression of Aβ and hyperphosphorylated tau proteins; improved glucose metabolism

[41]

APPswe/PS1∆E9 mice/male/10 months

Control groups: WT_Sed, AD_Sed

Intervention groups: WT_Run, AD_Run

3-month chronic voluntary wheel running

Increased glucose uptake; increased GLUT5 expression

[42]

Sprague–Dawley rats/male/10–12 weeks

Control group: no exercise

Intervention groups: forced treadmill exercise group and voluntary running-wheel exercise group

3-week chronic treadmill exercise/30 min each day, 5 days a week/exercise intensity not indicated;

3-week chronic voluntary wheel running

Enhanced glycolysis; increased levels of GLUT1, GLUT3, phosphofructokinase and lactate dehydrogenase proteins

[56]

Aβ oligomer-induced mice/male/8 weeks

Control groups: saline plus non-intervention group, Aβ oligomer plus non-intervention group

Intervention group: Aβ oligomer plus involuntary and voluntary running group

4-week regular involuntary treadmill running/50 min each day, 6 days a week/exercise intensity not indicated;

4-week chronic voluntary wheel running

Increased glutamate metabolism, glucose metabolism and tricarboxylic acid cycle

[60]

APPswe/PS1∆E9 mice/male/5 months

Control groups: SED-Con, SED-APP/PS1

Intervention groups: EXE-Con, EXE-APP/PS1

5-month chronic treadmill exercise/30 min each day, 6 days a week/exercise intensity not indicated

APP, BACE1 and RAGE protein levels were decreased; ADAM10 protein level was increased; Aβ was reduced

[75]

Tg2576 mice/male/

3 months

Control group: sedentary control group

Intervention group: low and high intensity exercise training group

12-week chronic treadmill running/1 h each day, 5 days a week/low and high intensity

Increased levels of NEP, IDE, MMP9, LRP1 and HSP70; increased Aβ degradation and efflux

[93]

Wistar rats/male/

8 weeks

Control groups: Aβ injection group, sham injection group

Intervention groups: Aβ injection + exercise group, sham injection + exercise group

4-week chronic treadmill exercise/5 days a week/mild to moderate intensity

Increased ABCA1 mRNA expression; improved brain lipid metabolism

[105]

APPswe/PS1∆E9 mice/male/3 months

Control group: transgenic control group

Intervention groups: transgenic 45%–55% and 60%–70% maximal oxygen uptake exercise groups

5-month chronic treadmill training/30 min each day, 5 days a week/medium and low intensity

RXR and total cholesterol decreased; LXR, LRP1/LDLR, APOE and ABCA1 levels were upregulated; lipid metabolism increased

[106]

APPswe/PS1∆E9 mice/male/3 months

Control groups: WT-NT, AD-NT

Intervention groups: WT-T, AD-T

12-week regular treadmill exercise training/45 min each day, 5 days a week/moderate intensity

Decreased cholesterol, BACE1 and flotillin1 levels; decreased number of lipid rafts; increased ADAM10 level

[116]

APPswe/PS1∆E9 mice/male/7 months

Control groups: SED-Con, SED-APP/PS1

Intervention groups: EXE-Con, EXE-APP/PS1

4-week chronic involuntary treadmill running combined with swimming/40 min each day, 6 days a week/mild to moderate intensity

Improved lipid metabolism and amino acid metabolism

[118]

5xFAD transgenic mice/male/6 weeks

Control group: sedentary group

Intervention group: voluntarily exercise group

6-month chronic voluntary wheel running

Decreased TfR, DMT1, ferritin, IL-6, STAT3, JAK1 and hepcidin levels; reduced iron overload

[131]

  1. EXE-APP/PS1: Exercise-trained APP/PS1 transgenic mice; EXE-Con: Exercise-trained wild-type control mice; SED-APP/PS1: Sedentary APP/PS1 transgenic mice; SED-Con: Sedentary wild-type control mice; NTg-C: Nontransgenic controls; NTg-TE: Non-transgenic exercise; Tg-C: Transgenic controls; Tg-TE: Transgenic exercise; WT-NT: Wild-type mice group with no exercise; WT-T: Wild-type mice group with regular exercise; AD-NT: APP/PS1 mice group with no exercise; AD-T: APP/PS1 mice group with regular exercise; WT_Sed: Wild-type mice sedentary group; AD_Sed: APP/PS1 mice sedentary group; WT_Run: Wild-type mice running group; AD_Run: APP/PS1 mice running group; VO2max: Maximal oxygen consumption