Table 4.

Included rodent studies combining physical exercise and nutritional intervention.

Study	Subjects	Intervention	Groups	Outcome measure	Results
Bhattacharya et al., 2015	N = 91; male BALB/cJ mice Age: 10 weeks	Running wheel 1.49 mg of EGCG per g diet 3.34 mg of B-ALA per g diet	Exe, sed, B-ALA: exe or sed, EGCG: exe or sed, B-ALA + EGCG: exe or sed N = 11–12 per group	Fear conditioning (contextual and cued) BrdU staining	Exe increased duration of freezing (contextual) Exe approx. 4-fold greater duration of freezing behavior than sed (cued) No effect of diet or interaction between diet and exercise Exe increased total number of BrdU+ cells in the granule layer of the denate gyrus approx. 4 fold over sed No effect of diet or interaction between diet and exercise
Cechella et al., 2014a	Male wistar rats	Swim training: 20 min, 5×/week 1 ppm of diphenyl diselenide (selenium) 5 weeks	Exe (I), selenium (II), exe + selenium (III), adult control (IV), aged control (V) N = 4–6 per groups	ORT OLT	Short term memory: (I)+(II) improved compared to (V), (III) better than all other groups Long term memory: (II)+(III) better than control groups (II) better than aged control, (I) + (III) better than control groups
				CREB and Akt in hippocampus	pAkt/ Akt: same for (I)+(III)+(IV)+(V), (I) higher than control groups pCREB/ CREB: (I)+(II)+(III) better than aged control
Cechella et al., 2014b	N = 30; male wistar rats	Swim training: 20 min, 5×/week 1 ppm of diphenyl diselenide (selenium) 5 weeks	Exe (I), selenium (II), exe + selenium (III), adult control (IV), aged control (V) N = 4–6 per groups	ORT	Short term memory: (I)+(II)+(III) better than control groups, (III) shows the best results Long term memory: (I)+(II)+(III) better than aged control, (I) better than adult control
				OLT	(I)+(II)+(IIII) better than aged control
				CREB in hippocampus	pCREB/CREB: (I)+(II) better than control groups
Chytrova et al., 2010	N = 24; adult male Sprague-Dawley rats	Running wheel DHA enriched diet 12 days	RD + sed (I), DHA + sed (II), RD + exe (III), DHA + exe (IV) N = 6 per group	Synaptic proteins in hippocampus	NR2B: sig. increase for (II)+(III)+(IV), greatest effect for (IV) compared to (III) STX-3 and GAP-43: sig increase for (II)+(III)+(IV), greatest effect for (IV)
				MWM	Latency: (II)+(III)+(IV) decreased compared to (I)
Gomez-Pinilla and Ying, 2010	N = 24; male Sprague-Dawley rats	Running wheel DHA enriched diet 2 weeks	RD + sed (I), DHA + sed (II), RD + exe (III), DHA + exe (IV) N = 6 per group	Hip and Hyp dissection	Leptin: Hyp: increase for (II)+(III)+(IV), greatest for (IV), Hip: increase for (II) Ghrelin: Hyp: increase for (III), Hip: increase for (II)+(III) p-AMPK: Hyp: decrease for (II)+(III)+(IV), Hip: increase for (II)+(III)+(IV) SIRT: Hyp: increase for (II)+(III)+(IV), greatest for (IV), Hip: increase for (II)+(III)+(IV) Glucocorticoid receptor: Hyp: decrease for (II), increase for (III), Hip: increase for (II)+(III)+(IV) 11-beta-HSD1: Hyp: increase for (II), Hip: increase for (II)+(III)+(IV)
Hansalik et al., 2006	N = 200; male Sprague-Dawley rats	Running wheel Treadmill: 20 min, 5×/week CR 13 months	Baseline (age: 5 months) (I), exe (TM) (II), exe (RW) + CR (III), sed + CR (IV), sed1 (one rat, one cage) (V), sed4 (four rats, one cage) (VI)	MWM	Learning and short term memory: no effects comparing various intervention groups at age 10 and 18 months
Jacotte-Simancas et al., 2013	N = 62; male wistar rats Age: 2 months	Running wheel Epinephrine: 0.01 or 0.05 mg/kg	Sed (I), sed + 0.01 ep (II), sed + 0.05 ep (III), exe (IV), exe + 0.01 ep (V), exe + 0.05 ep (VI)	Barnes maze	Distance: (IV)+(V)+(VI) sig. shorter than (I)+(II)+(III) Latency: no sig. results
Khabour et al., 2010	Male wistar rats Age: 5 months	Voluntary exercise CR 6 weeks	Sed (I), CR (II), exe (III), exe + CR (IV) N = 10–13 per group	RAWM	Spatial learning and memory formation: (IV)+(III) enhanced compared to (I)+(II), no effect of CR
				Hippocampal BDNF	BDNF: (IV)+(III) sig. higher levels compared to (I)+(II), no effect of CR
Khabour et al., 2013	N = 92; young wistar male rats	Swimming: 60 min, 5×/week CR 6 weeks	Sed (I), CR (II), exe (III), exe + CR (IV) N = 15 per group	RAWM Hippocampal BDNF	Spatial learning and memory formation: (IV)+(III) enhanced learning/memory compared to (I)+(II), no effect of CR (IV)+(III) sig. higher levels compared to (I)+(II) no effect of CR
Rachetti et al., 2013	N = 45; adult wistar rats	Treadmill: 30 min, 5×/week (until age of 27 days) Fish oil capsules Length: prenatal to 10 months	Exe (I), exe + fish (II), control (III), control + fish (VI) N = 11–12 per group	Open field test	(VI) decrement in location during 2nd exposure compared to the other groups
				ORT	Test session: all groups explored sig. more the novel object compared to familiar object, Re-test session: (II) explored sig. more the novel object compared to familiar object
				Plus maze discriminative avoidance task	(I)+(II) discriminated the aversive from non-aversive arms and spent sig. less time in aversive arm
Strasser et al., 2006	Male Sprague-Dawley rats	Running wheel Treadmill: 20 min, 5×/week CR 13 months	Baseline (age: 5 months) (I), exe (TM) (II), exe (RW) + CR (III), sed + CR (IV), sed1 (one rat, one cage) (V), sed4 (four rats, one cage) (VI)	BDNF in parietotemporal cortex	Decrease for (V), increase for (VI), highest values for (VI)
Wu et al., 2008	N = 24; Sprague-Dawley rats	Running wheel DHA enriched diet 12 days	RD + sed (I), DHA + sed (II), RD + exe (III), DHA + exe (IV)	MWM BDNF, Synapsin I, CREB, Akt, CaMKII Oxidative proteins	Latency: (II)+(III)+(IV) shorter than (I), (IV) shorter than (II)+(III) (II)+(III) increased values and even more in (IV) (II)+(III) reduced oxidized protein and even more in (IV)

The studies are reported by subjects, intervention, groups, outcome measure, and results. 11betaHSD1, 11-beta-hydroxysteroid-dehydrogenase type 1; B-ALA, Beta-alanine; BDNF, Brain-derived neurotrophic factor; BrdU, Bromodeoxyuridine; CaMKII, Calmodulin-dependent protein kinase II; CR, Calorie restriction; CREB, Cyclic adenosine monophosphate response element-binding protein; DHA, Docosahexaenoic acid; EGCG, Epigallocatechin gallate; Ep, Epinephrine; Exe, Exercise; GAP-43, Growth associated protein 43; Hip, Hippocampus; Hyp, Hypothalamus; MWM, Morris Water Maze; NR2B, N-methyl-D-aspartate Receptor 2B; OLT, Object Location Test; ORT, Object Recognition Test; p-AMPK, Phospho-adenosine monophosphate-activated protein kinase; pCREB, Phosphorylated cyclic adenosine monophosphate response element-binding protein; RAWM, Radial Arm Water Maze; RD, Restricted diet; RW, Running wheel; Sed, Sedentary; SIRT, Sirtuin; STX, Syntaxins; TM, Treadmill.