Table 1.

Effects of physical exercise on brain metabolism in animal models

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]

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; VO_2max: Maximal oxygen consumption