Abstract

Infancy and childhood are periods of physical and cognitive development that are vulnerable to disruption by dehydration; however, the effects of dehydration on cognitive development during the periods have not yet been fully elucidated. Thus, the present study used a murine model to examine the effects of sustained dehydration on physical growth and cognitive development. Three-week-old C57BL/6J mice were provided either ad libitum (control group) or time-limited (15 min/day; dehydration group) access to water for 4 weeks. Physical growth was examined via a dual-energy X-ray absorptiometry whole-body scan, and cognitive development was assessed using the Barnes maze test. RNA-sequencing and qPCR analyses were carried out to assess the hippocampal transcriptome and the expression of key neurotrophic factors, respectively. These analyses showed that dehydrated mice exhibited a reduced body mass and tail length, and they spent four times longer completing the Barnes maze test than control mice. Moreover, dehydration significantly dysregulated long-term potentiation signaling and specifically decreased hippocampal brain-derived neurotrophic factor (Bdnf) expression. Collectively, these data confirm dehydration inhibits physical growth and suggest that it impairs cognitive development by altering the hippocampal transcriptional network in young mice; thus, they highlight the importance of water as a vital nutrient for optimal growth and development during infancy and childhood.

Highlights

  • Water in the body acts as a solvent to carry nutrients, a reactant and product during metabolism, and a major constituent of both cells and tissues [1]; optimal hydration is essential to enable a range of normal physiological functions required to maintain organismal health [2]

  • No significant difference in energy intake was observed between the CON and DEH mice during the experimental period (Figure S1a), and we noted that plasma glucose levels were significantly (20%) lower (p < 0.05) in the DEH than the CON group, this change was not accompanied by any significant changes to plasma insulin levels (Figure S1b,c)

  • Previous studies generally either examined the acute effects of 24 and/or 48 h of dehydration using a complete water-deprivation model [26,27], or induced dehydration using heat- and exercise-exposure models [8,28,29]. Neither of these methodologies evaluate the effects of long-term dehydration induced by insufficient water intake; the present study aimed to examine the impacts of prolonged insufficient water intake on the physical and cognitive development

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Summary

Introduction

Water in the body acts as a solvent to carry nutrients, a reactant and product during metabolism, and a major constituent of both cells and tissues [1]; optimal hydration is essential to enable a range of normal physiological functions required to maintain organismal health [2]. Some previous studies have reported that fluid restriction negatively impacts short-term memory [7], while others have shown that mild dehydration improves short-term memory function [8]. The importance of water as an essential nutrient is well established, the mechanisms underlying the negative impacts of dehydration, especially on cognitive function, have not yet been fully elucidated. Finely controlled animal studies are urgently needed to further examine how inadequate daily water intake detrimentally impacts cognitive function. Children require a higher water intake/unit of body weight than adults because they have a higher body-water composition

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