Effects of β-Hydroxy β-Methylbutyrate Supplementation on Working Memory and Hippocampal Long-Term Potentiation in Rodents.

Alejandro Barranco,Ricardo Rueda,Llenalia Garcia,Maria Ramirez,Agnes Gruart,Jose Maria Delgado-Garcia

doi:10.3390/nu14051090

Alejandro Barranco, Ricardo Rueda + Show 4 more

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https://doi.org/10.3390/nu14051090

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Abstract

β-hydroxy β-methylbutyrate (HMB), a metabolite of the essential amino acid leucine, has been shown to preserve muscle mass and strength during aging. The signaling mechanism by which HMB elicits its favorable effects on protein metabolism in skeletal muscle is also preserved in the brain. However, there are only a few studies, all at relatively high doses, addressing the effect of HMB supplementation on cognition. This study evaluated the effects of different doses of HMB on the potentiation of hippocampal synapses following the experimental induction of long-term potentiation (LTP) in the hippocampus of behaving rats, as well as on working memory test (delayed matching-to-position, DMTP) in mice. HMB doses in rats were 225 (low), 450 (medium), and 900 (high) mg/kg body weight/day and were double in mice. Rats who received medium or high HMB doses improved LTP, suggesting that HMB administration enhances mechanisms related to neuronal plasticity. In the DMTP test, mice that received any of the tested doses of HMB performed better than the control group in the overall test with particularities depending on the dose and the task phase.

Highlights

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The aims of this study were: (1) to reproduce the effect of hydroxy β-methylbutyrate (HMB) on brain functionality using an automated system designed for behavioral studies in rodents (IntelliCage®, NewBehavior AG, Zurich, Switzerland) [23] using a behavioral task to assess the spatial working memory in animals (DMTP task) [24] (2) to test if HMB was able to affect long-term potentiation (LTP), an electrophysiological mechanism underlying synaptic plasticity and memory storage [25], and
The experiments were conducted in mice and rats for DMTP and LTP, respectively, because the equipment and experimental techniques were adapted to these species: IntelliCages are optimized for mice and the implantation of electrodes for LTP is easier in rats than in mice due to the size of the skull

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Cognitive decline is a normal process of aging, with some cognitive abilities, such as conceptual reasoning, processing speed, and memory, being more susceptible to this gradual decline [1–3]. Non-modifiable factors, like age, race and ethnicity, gender, and genetics are involved in this cognitive decline, several life-style interventions, including physical activities, cognitive training, and nutritional interventions, have been shown to have a positive impact [4,5]. Several studies have shown that maintaining a healthy diet could be associated with slower cognitive decline and reduced risk of Alzheimer’s disease [6]

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