Molecular Neurobiology

, Volume 55, Issue 4, pp 3408–3425 | Cite as

Glucose Can Epigenetically Alter the Gene Expression of Neurotrophic Factors in the Murine Brain Cells

  • Md Shamim HossainEmail author
  • Yutaka Oomura
  • Toshihiko Katafuchi


Glucose is believed to improve the memory in both human and mice, but the detailed insights were mostly elusive. In this study, we focused on two major neurotrophic factors, brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 1 (FGF1), which are believed to be associated with the memory enhancement and assessed their expressional regulation among the murine neuronal and glial cells. Our findings showed that the glucose administration increased phosphorylated Akt, phosphorylated CREB, exon 1- and exon 4-specific BDNF transcripts, and FGF1 transcripts that are associated with the epigenetic changes expected to open the chromatin and a reduction in histone deacetylase 2 (HDAC2) in neurons and astrocytes of the murine hippocampus. The glucose administration enhanced the long-term potentiation and the number of dendritic spines in the CA1 and CA3 subfields of hippocampus. The intrahippocampal injection of short hairpin RNA against TrkB canceled the glucose-mediated memory enhancement. Like the glucose, we also report that the HDAC inhibitor can enhance the memory through the BDNF-TrkB pathway but it targeted different brain cell populations to enhance the BDNF and FGF1 transcripts. In addition, the soluble FGF1 treatments significantly increased the BDNF expression in astrocytes and neurons, suggesting that the glucose-mediated induction of the neurotrophic factors could contribute to the memory. Our study provides the valuable insights, explaining the distinctive neuronal and glial cell regulation of the neurotrophic factors by glucose and HDAC inhibitor, which could likely explain how our brain cells can control the release of neurotrophic factors.


Glucose BDNF FGF1 TrkB SAHA Memory 



This study was supported by the JSPS Grant-in-Aid for Young Scientists (Wakate B) [16K19007] to M.S.H. and the JSPS KAKENHI Grant Number 22590225 to T.K. We would like to appreciate the valuable technical supports from the Research Support Center, Graduate School of Medical Sciences, Kyushu University. Special thanks go to Dr. Ako Niwase and Dr. Motoko Unoki for their critical corrections of English. We also thank Ayako Tajima for the technical assistance to perform the experiments.

Author Contributions

This study is designed by MSH, YO, and TK. TK helped to perform electrophysiology studies. MSH performed the in vitro and in vivo studies and analyzed the data. The manuscript is written by MSH and revised by TK and YO.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2017_578_MOESM1_ESM.pptx (282 kb)
Supplementary Figure S1 Recruitments of CREB and HDAC2 onto the BDNF and FGF1 promoters. (A) ChIP-semiquantitative PCR analysis using anti-CREB and anti-HDAC2 antibodies. The Neuro2A, A1 and MG6 cells were cultured in normal culture medium and the 500 μg cellular extracts were subjected to the ChIP assays. The PCR cycle was 35 X and the data represents three independent experiments (n = 3). For the input control, GAPDH primers were used and the PCR cycle was 24 X. (B) The cells were cultured in glucose free medium for 12 h followed by the low, L (2.5 mM) and High, H (7.0 mM) glucose treatments for 6 h. The ChIp assays using the anti-CREB antibody show the recruitments onto the indicated promoter regions. The GEM promoter was used as a CREB binding positive control. The data represents three independent experiments and the PCR cycle used was 35 X (n = 3). (C) In the same experimental protocol of panel B, the ChIP assays were performed with the antibody against HDAC2. The data represents three independent experiments and the L and H stands for Low and High glucose, respectively (n = 3). The input samples were checked for the quantity of the genomic DNA, using the GAPDH primers, used for the ChIP assays. (PPTX 281 kb)
12035_2017_578_MOESM2_ESM.pptx (72 kb)
Supplementary Figure S2 Swimming speed in the water maze tasks. (A) Swimming speeds measured in sh-Luc (n = 7) and sh-TrkB (n = 7) mice as described in Fig. 7C. The speeds were measured on the trail number 8. (B) The swimming speeds were measured on trial number 8 in sh-Luc and sh-TrkB groups treated with the water and glucose solution as described in Fig. 7E. (C) The swimming speeds of the probe tests as described in Fig. 7H. The data represents mean and standard error of means. Statistical analysis using Student’s t-test showed no significant (n.s.) differences between the two groups. (PPTX 72 kb)


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Md Shamim Hossain
    • 1
    Email author
  • Yutaka Oomura
    • 1
  • Toshihiko Katafuchi
    • 1
  1. 1.Department of Neuroinflammation and Brain Fatigue Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

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