Changes of hippocampal beta-alanine and citrulline levels are paralleling early and late phase of retrieval in the Morris Water Maze

Sase, Ajinkya; Dahanayaka, Sudath; Höger, Harald; Wu, Guoyao; Lubec, Gert

doi:10.1016/j.bbr.2013.04.033

Cited by 23 publications

(22 citation statements)

References 30 publications

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“…A recent study found B-ALA levels in the hippocampus of rats increased after a Morris water maze probe trial [42], consistent with a role for B-ALA in spatial memory retrieval. In addition, carnosine supplementation was shown to improve cognitive function in schizophrenic patients [43].…”

Section: Introductionsupporting

confidence: 57%

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

Bhattacharya¹,

Pence²,

Ossyra³

et al. 2015

Physiology & Behavior

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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.

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Section: Introductionsupporting

confidence: 57%

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

Bhattacharya¹,

Pence²,

Ossyra³

et al. 2015

Physiology & Behavior

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show abstract

“…β-ala was included because it has been shown to improve muscle function and decrease fatigue [33] and thus might indirectly (via increasing exercise capacity) improve cognition. In addition, a more direct role for β-ala has been suggested in the retrieval of spatial memory because hippocampal β-ala increases after a MWM probe trial [34]. …”

Section: Discussionmentioning

confidence: 99%

“…Less is known about the effect of β-ala on learning or memory. A recent study demonstrated an increase in β-ala in the hippocampus of rats at 5 minutes and 6 hours after a Morris water maze probe trial [34], a finding the authors speculate may indicate a role for β-ala in retrieval of spatial memory. β-ala is thought to act as a neurotransmitter in the hippocampus, is a structural intermediate between established amino acid neurotransmitters glycine and γ-aminobutyric acid (GABA), and is recognized by multiple receptors in the central nervous system (CNS) [32].…”

Section: Introductionmentioning

confidence: 99%

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

Gibbons

Pence

Petr

et al. 2014

Behavioural Brain Research

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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 mo) were given AIN-93M diet with or without EGCG (182 mg/kg/d) and β-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-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.

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“…L-Tyrosine showed higher levels in the pig (Li et al 2009), and L-tyrosine, L-serine and L-histidine levels were higher in the rat. Conversely, L-glutamine, GABA, L-valine and L-phenylalanine were lower in rats than in hamsters (Sase et al 2013). …”

Section: Discussionmentioning

confidence: 99%

Metabolism of amino acids differs in the brains of Djungarian hamster (P. sungorus) and Roborovskii hamster (P. roborovskii)

et al. 2014

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Djungarian hamster (P. sungorus) and Roborovskii hamster (P. roborovskii) belong to the same genus of phodopus. Roborovskii hamster shows high locomotor activity and low level of dopamine (DA) in the brain. Administration of L-tyrosine, a precursor of DA, decreases locomotor activity in Roborovskii hamsters. However, the amino acid metabolism in relation to the hyperactivity is not yet well known. In the present study, L- and D-amino acid concentrations in the brain, liver, and plasma in Djungarian and Roborovskii hamsters were investigated during day and night times to explain the possible difference in hyperactivity between them. Most of the examined amino acids were higher in the night time when hamsters are active compared to those in day time. L- and D-tyrosine concentrations were higher in the liver of Roborovskii hamsters than in Djungarian hamsters. Furthermore, brain concentration of D-tyrosine was higher in the Roborovskii than in Djungarian hamsters, but no significant difference was observed for L-tyrosine concentrations between the two species. These results suggest that the conversion of L-tyrosine to D-tyrosine in the brain of Roborovskii hamster may be higher than in Djungarian hamster, which may cause low DA concentration and hyperactivity in Roborovskii hamster. On the other hand, L- and D-serine, which are known as sedative factors, were lower in Roborovskii hamsters than Djungarian hamster. These results suggest that species-specific regulation in amino acid metabolism may contribute to hyperactivity in Roborovskii hamsters.

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Changes of hippocampal beta-alanine and citrulline levels are paralleling early and late phase of retrieval in the Morris Water Maze

Cited by 23 publications

References 30 publications

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

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

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

Metabolism of amino acids differs in the brains of Djungarian hamster (P. sungorus) and Roborovskii hamster (P. roborovskii)

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