Differential effects of excess high-fructose corn syrup on the DNA methylation of hippocampal neurotrophic factor in childhood and adolescence.

Consumption of fructose-containing beverages such as high-fructose corn syrup (HFCS) is increasing, raising concerns about the negative effects of excessive fructose intake. A recent report indicated that excess HFCS intake impairs hippocampal function. In this study, we focused on neurotrophic fact...

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Main Authors: Itsuki Kageyama, Hiroya Yamada, Eiji Munetsuna, Mirai Yamazaki, Yoshitaka Ando, Genki Mizuno, Ryosuke Fujii, Yuki Nouchi, Takuya Wakasugi, Tomohide Sakakibara, Atsushi Teshigawara, Hiroaki Ishikawa, Yohei Shimono, Koji Suzuki, Shuji Hashimoto, Koji Ohashi
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0270144
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author Itsuki Kageyama
Hiroya Yamada
Eiji Munetsuna
Mirai Yamazaki
Yoshitaka Ando
Genki Mizuno
Ryosuke Fujii
Yuki Nouchi
Takuya Wakasugi
Tomohide Sakakibara
Atsushi Teshigawara
Hiroaki Ishikawa
Yohei Shimono
Koji Suzuki
Shuji Hashimoto
Koji Ohashi
author_facet Itsuki Kageyama
Hiroya Yamada
Eiji Munetsuna
Mirai Yamazaki
Yoshitaka Ando
Genki Mizuno
Ryosuke Fujii
Yuki Nouchi
Takuya Wakasugi
Tomohide Sakakibara
Atsushi Teshigawara
Hiroaki Ishikawa
Yohei Shimono
Koji Suzuki
Shuji Hashimoto
Koji Ohashi
author_sort Itsuki Kageyama
collection DOAJ
description Consumption of fructose-containing beverages such as high-fructose corn syrup (HFCS) is increasing, raising concerns about the negative effects of excessive fructose intake. A recent report indicated that excess HFCS intake impairs hippocampal function. In this study, we focused on neurotrophic factors (NFs) in the hippocampus from the viewpoint of epigenetics to clarify the adverse effects of fructose. We analyzed the effects of HFCS intake on hippocampal function in three age categories: childhood and adolescence (postnatal day (PD) 21-60), young adulthood (PD60-100), and late adulthood (PD100-140). For the experiments, male Sprague-Dawley rats were divided into three age categories, the control group was received distilled water and the HFCS group was received 20% HFCS solution for 40 days in each period. We analyzed mRNA and protein levels for qPCR and western blotting, respectively, of a hippocampal NF, brain-derived neurotrophic factor (Bdnf). HFCS consumption reduced hippocampal Bdnf mRNA and protein expressions in childhood and adolescence. Moreover, pyrosequencing assays revealed increased DNA methylation at the Bdnf promoter in childhood and adolescence. This Bdnf levels reduction may be due to hypermethylation of the promoter regions. It should be noted that this phenomenon was observed only in childhood and adolescence fructose consumption. Our results indicate that the sensitivity of the hippocampus to fructose may vary with age. This study provides insight into the adverse effects of excessive HFCS consumption on the hippocampus in children.
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spelling doaj.art-5bc24816f376479fb0f4b18fd8a48b632022-12-22T03:00:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01176e027014410.1371/journal.pone.0270144Differential effects of excess high-fructose corn syrup on the DNA methylation of hippocampal neurotrophic factor in childhood and adolescence.Itsuki KageyamaHiroya YamadaEiji MunetsunaMirai YamazakiYoshitaka AndoGenki MizunoRyosuke FujiiYuki NouchiTakuya WakasugiTomohide SakakibaraAtsushi TeshigawaraHiroaki IshikawaYohei ShimonoKoji SuzukiShuji HashimotoKoji OhashiConsumption of fructose-containing beverages such as high-fructose corn syrup (HFCS) is increasing, raising concerns about the negative effects of excessive fructose intake. A recent report indicated that excess HFCS intake impairs hippocampal function. In this study, we focused on neurotrophic factors (NFs) in the hippocampus from the viewpoint of epigenetics to clarify the adverse effects of fructose. We analyzed the effects of HFCS intake on hippocampal function in three age categories: childhood and adolescence (postnatal day (PD) 21-60), young adulthood (PD60-100), and late adulthood (PD100-140). For the experiments, male Sprague-Dawley rats were divided into three age categories, the control group was received distilled water and the HFCS group was received 20% HFCS solution for 40 days in each period. We analyzed mRNA and protein levels for qPCR and western blotting, respectively, of a hippocampal NF, brain-derived neurotrophic factor (Bdnf). HFCS consumption reduced hippocampal Bdnf mRNA and protein expressions in childhood and adolescence. Moreover, pyrosequencing assays revealed increased DNA methylation at the Bdnf promoter in childhood and adolescence. This Bdnf levels reduction may be due to hypermethylation of the promoter regions. It should be noted that this phenomenon was observed only in childhood and adolescence fructose consumption. Our results indicate that the sensitivity of the hippocampus to fructose may vary with age. This study provides insight into the adverse effects of excessive HFCS consumption on the hippocampus in children.https://doi.org/10.1371/journal.pone.0270144
spellingShingle Itsuki Kageyama
Hiroya Yamada
Eiji Munetsuna
Mirai Yamazaki
Yoshitaka Ando
Genki Mizuno
Ryosuke Fujii
Yuki Nouchi
Takuya Wakasugi
Tomohide Sakakibara
Atsushi Teshigawara
Hiroaki Ishikawa
Yohei Shimono
Koji Suzuki
Shuji Hashimoto
Koji Ohashi
Differential effects of excess high-fructose corn syrup on the DNA methylation of hippocampal neurotrophic factor in childhood and adolescence.
PLoS ONE
title Differential effects of excess high-fructose corn syrup on the DNA methylation of hippocampal neurotrophic factor in childhood and adolescence.
title_full Differential effects of excess high-fructose corn syrup on the DNA methylation of hippocampal neurotrophic factor in childhood and adolescence.
title_fullStr Differential effects of excess high-fructose corn syrup on the DNA methylation of hippocampal neurotrophic factor in childhood and adolescence.
title_full_unstemmed Differential effects of excess high-fructose corn syrup on the DNA methylation of hippocampal neurotrophic factor in childhood and adolescence.
title_short Differential effects of excess high-fructose corn syrup on the DNA methylation of hippocampal neurotrophic factor in childhood and adolescence.
title_sort differential effects of excess high fructose corn syrup on the dna methylation of hippocampal neurotrophic factor in childhood and adolescence
url https://doi.org/10.1371/journal.pone.0270144
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