Voluntary wheel running, but not a diet containing (-)-epigallocatechin-3-gallate and β-alanine, improves learning, memory and hippocampal neurogenesis in aged mice - PubMed (original) (raw)

doi: 10.1016/j.bbr.2014.05.049. Epub 2014 Jul 5.

Brandt D Pence 2, Geraldine Petr 1, Jessica M Ossyra 3, Houston C Mach 3, Tushar K Bhattacharya 3, Samuel Perez 3, Stephen A Martin 2, Robert H McCusker 4, Keith W Kelley 4, Justin S Rhodes 5, Rodney W Johnson 4, Jeffrey A Woods 6

Affiliations

Voluntary wheel running, but not a diet containing (-)-epigallocatechin-3-gallate and β-alanine, improves learning, memory and hippocampal neurogenesis in aged mice

Trisha E Gibbons et al. Behav Brain Res. 2014.

Abstract

Aging is associated with impaired learning and memory accompanied by reductions in adult hippocampal neurogenesis and brain expression of neurotrophic factors among other processes. Epigallocatechin-3-gallate (EGCG, a green tea catechin), β-alanine (β-ala, the precursor of carnosine), and exercise have independently been shown to be neuroprotective and to reduce inflammation and oxidative stress in the central nervous system. We hypothesized that EGCG, β-ala supplementation or exercise alone would improve learning and memory and increase neurogenesis in aged mice, and the combined intervention would be better than either treatment alone. Male Balb/cByJ mice (19 months) were given AIN-93M diet with or without EGCG (182mg/kg/d) and β-ala (417mg/kg/d). Half of the mice were given access to a running wheel (VWR). The first 10 days, animals received 50mg/kg bromodeoxyuridine (BrdU) daily. After 28 days, learning and memory was assessed by Morris water maze (MWM) and contextual fear conditioning (CFC). Brains were collected for immunohistochemical detection of BrdU and quantitative mRNA expression in the hippocampus. VWR increased the number of BrdU cells in the dentate gyrus, increased expression of brain-derived neurotrophic factor, decreased expression of the inflammatory cytokine interleukin-1β, and improved performance in the MWM and CFC tests. The dietary intervention reduced brain oxidative stress as measured by 4-hydroxynonenal in the cerebellum, but had no effect on BrdU labeling or behavioral performance. These results suggest that exercise, but not a diet containing EGCG and β-ala, exhibit pro-cognitive effects in aged mice when given at these doses in this relatively short time frame.

Keywords: Aging; Cognition; Diet; Exercise; Learning; Mice.

Copyright © 2014 Elsevier B.V. All rights reserved.

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Figures

Figure 1

Figure 1. Experimental timeline

Experimental intervention (dietary and exercise) continued through duration of study. Abbreviations: Morris water maze (MWM), contextual fear conditioning (CFC), novel context (NC), bromodeoxyuridine (Brdu).

Figure 2

Figure 2. Exercise, but not EGCG/β-ala, decreases latency during a test of spatial learning of aged mice in the Morris water maze

All mice learned the task as evidenced by a significantly shorter path length to the hidden platform over time (1b). VWR mice found the platform faster later in the acquisition period (1b), this effect was most probably due to significantly faster swim speeds (1c). There was no main effect of the diet or diet × VWR or diet × VWR × time interactions for any of the variables. Data are shown as the mean ± SEM. *p < 0.05 for the main effect of exercise. n = 12, 14, 15 and 15 for Con-Sed, EGCG/β-ala-Sed, Con-VWR and EGCG/β-ala-VWR, respectively.

Figure 3

Figure 3. Exercise, but not EGCG/β-ala, enhances reference memory on probe trials in the Morris water maze

On both Days 5 (2a) and 7 (2b), VWR mice crossed the original location of the platform more often than sedentary mice. Data are shown as the mean ± SEM. *p < 0.05 for the main effect of exercise. n = 12, 13, 14 and 15 for Con-Sed, EGCG/β-ala-Sed, Con-VWR and EGCG/β-ala-VWR, respectively.

Figure 4

Figure 4. Exercise but not EGCG/β-ala improves learning in the contextual fear conditioning test

In pre-conditioned animals, VWR resulted in a significant increase in time spent frozen when re-introduced into the original context 24 hrs later when compared to sedentary aged mice (5a). There was no effect of the diet or a diet × VWR interaction. In the novel context (5b), VWR increased freezing in the pre- and post-tone conditions with no diet or diet × VWR interaction. There were no significant group differences in the tone condition. Data are shown as the mean ± SEM. *p < 0.05 for the main effect of exercise. n = 10, 11, 11 and 10 for Con-Sed, EGCG/β-ala-Sed, Con-VWR and EGCG/β-ala-VWR, respectively.

Figure 5

Figure 5. VWR, but not EGCG and β-ala, increases hippocampal cell proliferation

Data are shown as the mean ± SEM. *p < 0.05 for the main effect of exercise. n = 12, 13, 14 and 15 for Con-Sed, EGCG/β-ala-Sed, Con-VWR and EGCG/β-ala-VWR, respectively.

Figure 6

Figure 6. A diet containing EGCG and β-ala reduces 4-HNE in the cerebellum of aged mice

Data are represented as means ± SEM. *p < 0.05 for the main effect of diet. n = 9, 10, 9, 11 for Con-Sed, Con-VWR, EGCG/β-ala-Sed and EGCG/β-ala-VWR, respectively.

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