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

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), beta-alanine (beta-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, beta-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 (182 mg/kg/d) and beta-ala (417 mg/kg/d). Half of the mice were given access to a running wheel (VWR). The first 10 days, animals received 50 mg/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-1 beta, 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 beta-ala, exhibit pro-cognitive effects in aged mice when given at these doses in this relatively short time frame. (C) 2014 Elsevier B.V. All rights reserved.