Exercise but not (–)-epigallocatechin-3-gallate or β-alanine enhances physical fitness, brain plasticity, and behavioral performance in mice

Abstract

Nutrition and physical exercise can enhance cognitive function but the specific combinations of dietary bioactives that maximize pro-cognitive effects are not known nor are the contributing neurobiological mechanisms. Epigallocatechin-3-gallate (EGCG) is a flavonoid constituent of many plants with high levels found in green tea. EGCG has anti-inflammatory and anti-oxidant properties and is known to cross the blood brain barrier where it can affect brain chemistry and physiology. β-alanine (B-ALA) is a naturally occurring β–amino acid that could increase cognitive functioning by increasing levels of exercise via increased capacity of skeletal muscle, by crossing the blood brain barrier and acting as a neurotransmitter, or by free radical scavenging in muscle and brain after conversion into carnosine. The objective of this study was to determine the effects of EGCG (∼ 250 mg/kg/day), B-ALA (∼550 mg/kg/day), and their combination with voluntary wheel running exercise on the following outcome measures: body composition, time to fatigue, production of new cells in the granule layer of the dentate gyrus of the hippocampus as a marker for neuronal plasticity, and behavioral performance on the contextual and cued fear conditioning tasks, as measures of associative learning and memory. Young adult male BALB/cJ mice approximately 2 months old were randomized into 8 groups varying the nutritional supplement in their diet and access to running wheels over a 39 day study period. Running increased food intake, decreased fat mass, increased time to exhaustive fatigue, increased numbers of new cells in the granule layer of the hippocampus, and enhanced retrieval of both contextual and cued fear memories. The diets had no effect on their own or in combination with exercise on any of the fitness, plasticity, and behavioral outcome measures other than B-ALA decreased percent body fat whereas EGCG increased lean body mass slightly. Results suggest that, in young adult BALB/cJ mice, a 39 day treatment of exercise but not dietary supplementation with B-ALA or EGCG, enhances measures of fitness, neuroplasticity and cognition.

d-Galactose High-Dose Administration Failed to Induce Accelerated Aging Changes in Neurogenesis, Anxiety, and Spatial Memory on Young Male Wistar Rats

“…61 The different methods for measuring neurogenesis, different strains of rodents used, and the different doses and administration modes of EGCG can justify these differing results, but additional research is needed to identify the main parameters explaining these discrepancies. 59 Unfortunately, we could not advance further information about the effects of EGCG oral administration (approximately 200 mg/kg per day) on neurogenesis on accelerated aged rats due to the lack of aging effects of d-galactose in the current experiment.…”

“…30 The same research group also found recently that oral administration of EGCG (approximately 250 mg/day) in 2-month-old male BALB/cJ mice did not improve the number of new cells in the dentate gyrus and did not ameliorate behavioral performance. 59 On the contrary, it was reported that 2 5 mg/kg per day EGCG gavage administration during 4 weeks enhanced cell proliferation and increased the number of neuroblasts in 2-month-old C57BL/6J mice dentate gyrus. 25 Also, oral administration of 270 mg/kg per day EGCG in male Wistar rats for 26 weeks enhanced neurogenesis and presented anti-oxidative activity.…”

Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice

“…Beta-alanine is not only a potential neurotransmitter at glycine receptors but also a constituent of carnosine and an inhibitor of taurine transport; these biological actions suggest that the level of beta- alanine in the hippocampus is probably involved in spatial memory retrieval [38]. Although no clear conclusion can be drawn [18, 29, 39], our results were consistent with recent studies that have demonstrated that the levels of valine and total alanine were decreased in either the serum or the cerebral gray matter of AD patients [40-42]. The lower levels of these metabolites provided some new evidence regarding the confusing role of lipids and amino acids in AD.…”

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

“…At a behavioural level, improvements in spatial learning and memory, associative learning and recognition memory have all been observed in animals following exercise training. Mice housed with a running wheel perform better in the MWM compared to their sedentary counterparts (Clark et al, 2008;Gibbons et al, 2014;Mustroph et al, 2012), while exercising mice also outperformed their sedentary counterparts in the contextual fear conditioning task (Bhattacharya et al, 2015;Clark et al, 2008;Gibbons et al, 2014). Data from our laboratory has demonstrated that rats trained on a treadmill perform better than their sedentary counterparts in the novel object recognition and object displacement tasks of recognition and spatial memory respectively (Griffin et al, 2009).…”