Excess maternal fructose consumption impairs hippocampal function in offspring via epigenetic modification of BDNF promoter

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Abstract

Recent increases in fructose consumption have raised concerns about the potential adverse in-tergenerational effects of excess fructose intake. In the present study, we investigated whether excess maternal fructose intake affects hippocampal function in offspring. Female Sprague-Dawley rats were divided into 3 experimental groups: one group received distilled water, one group received 20% fructose water, and one group received 20% glucose water in addition to standard chow during gestation and lactation. Hippocampal function of offspring was evaluated by using novel object recognition and fear conditioning tests. Impaired cognitive performance was observed in the offspring of fructose-fed dams at postnatal d 60, potentially a result of decreased hippocampal neurogenesis. Real-time PCR analysis demonstrated that offspring from fructose-fed dams exhibited decreased brain-derived neurotrophic factor (BDNF) gene expression, whereas pyrosequencing assays revealed increased DNA methylation at the BDNF promoter. The potential association between BDNF transcription and levels of DNA methylation was confirmed on the basis of luciferase activity. Furthermore, longitudinal analysis revealed that increased methylation of the BDNF promoter region was maintained at least until rats reached maturity. These results indicate that epigenetic changes associated with BDNF may underlie hippocampal dysfunction that is induced by early-life exposure to excess maternal fructose consumption.

Original languageEnglish
Pages (from-to)2549-2562
Number of pages14
JournalFASEB Journal
Volume32
Issue number5
DOIs
Publication statusPublished - 01-05-2018

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Brain-Derived Neurotrophic Factor
Fructose
Epigenomics
Mothers
DNA Methylation
Dams
Water
Rats
Methylation
Neurogenesis
Object recognition
Transcription
Luciferases
Lactation
Genetic Promoter Regions
Gene expression
Fear
Sprague Dawley Rats
Real-Time Polymerase Chain Reaction
Assays

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

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title = "Excess maternal fructose consumption impairs hippocampal function in offspring via epigenetic modification of BDNF promoter",
abstract = "Recent increases in fructose consumption have raised concerns about the potential adverse in-tergenerational effects of excess fructose intake. In the present study, we investigated whether excess maternal fructose intake affects hippocampal function in offspring. Female Sprague-Dawley rats were divided into 3 experimental groups: one group received distilled water, one group received 20{\%} fructose water, and one group received 20{\%} glucose water in addition to standard chow during gestation and lactation. Hippocampal function of offspring was evaluated by using novel object recognition and fear conditioning tests. Impaired cognitive performance was observed in the offspring of fructose-fed dams at postnatal d 60, potentially a result of decreased hippocampal neurogenesis. Real-time PCR analysis demonstrated that offspring from fructose-fed dams exhibited decreased brain-derived neurotrophic factor (BDNF) gene expression, whereas pyrosequencing assays revealed increased DNA methylation at the BDNF promoter. The potential association between BDNF transcription and levels of DNA methylation was confirmed on the basis of luciferase activity. Furthermore, longitudinal analysis revealed that increased methylation of the BDNF promoter region was maintained at least until rats reached maturity. These results indicate that epigenetic changes associated with BDNF may underlie hippocampal dysfunction that is induced by early-life exposure to excess maternal fructose consumption.",
author = "Mirai Yamazaki and Hiroya Yamada and Eiji Munetsuna and Hiroaki Ishikawa and Genki Mizuno and Takao Mukuda and Akihiro Mouri and Toshitaka Nabeshima and Kuniaki Saito and Koji Suzuki and Shuji Hashimoto and Koji Ohashi",
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AU - Yamazaki, Mirai

AU - Yamada, Hiroya

AU - Munetsuna, Eiji

AU - Ishikawa, Hiroaki

AU - Mizuno, Genki

AU - Mukuda, Takao

AU - Mouri, Akihiro

AU - Nabeshima, Toshitaka

AU - Saito, Kuniaki

AU - Suzuki, Koji

AU - Hashimoto, Shuji

AU - Ohashi, Koji

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Recent increases in fructose consumption have raised concerns about the potential adverse in-tergenerational effects of excess fructose intake. In the present study, we investigated whether excess maternal fructose intake affects hippocampal function in offspring. Female Sprague-Dawley rats were divided into 3 experimental groups: one group received distilled water, one group received 20% fructose water, and one group received 20% glucose water in addition to standard chow during gestation and lactation. Hippocampal function of offspring was evaluated by using novel object recognition and fear conditioning tests. Impaired cognitive performance was observed in the offspring of fructose-fed dams at postnatal d 60, potentially a result of decreased hippocampal neurogenesis. Real-time PCR analysis demonstrated that offspring from fructose-fed dams exhibited decreased brain-derived neurotrophic factor (BDNF) gene expression, whereas pyrosequencing assays revealed increased DNA methylation at the BDNF promoter. The potential association between BDNF transcription and levels of DNA methylation was confirmed on the basis of luciferase activity. Furthermore, longitudinal analysis revealed that increased methylation of the BDNF promoter region was maintained at least until rats reached maturity. These results indicate that epigenetic changes associated with BDNF may underlie hippocampal dysfunction that is induced by early-life exposure to excess maternal fructose consumption.

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