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

Abstract

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.

Shengui Sansheng San Ameliorates Cerebral Energy Deficiency via Citrate Cycle After Ischemic Stroke

“…Therefore, the stabilized cerebral energy provision relies on the regular glucose metabolism. As a major energy substrate, glucose is almost fully oxidized in brain, which not only supplies ATP for neuronal and non-neuronal cellular survival, but also can be as precursor for neurotransmitters biosynthesis (Dienel, 2012; Harris et al, 2012; Howarth et al, 2012; Mergenthaler et al, 2013; Hossain et al, 2018). When cerebral ischemia occurs, the provision of glucose is insufficient, which will cause neurons necrosis in ischemic central region within a few minutes and the damage gradually extends to the surrounding zone (Dirnagl et al, 1999; Mergenthaler et al, 2004).…”

Glucose and fructose directly stimulate brain-derived neurotrophic factor gene expression in microglia

“…Inconsistent findings regarding the effect of glucose on Bdnf gene expression in microglial cell lines may be explained by the difference in the experimental design between the two studies. In the study by Hossain et al [15], the effect of glucose was examined at lower concentrations (2.5 vs. 7 mmol/l) compared with those in the present study (17.5 vs. 25 mmol/l). MG6 cell line was established from mouse whole brain and immortalized by viral transduction with oncogenes, whereas SIM-A9 is a spontaneously immortalized cell line obtained from mouse cerebral cortex [10,16].…”

“…Moreover, 2-DG treatment reduced levels of pan-Bdnf mRNA in primary cultured cells from rat mediobasal hypothalamus [14]. It was also reported that increased glucose concentration enhances pan-Bdnf mRNA expression in neuronal and astrocyte cell lines, but not in microglial MG6 cells [15]. Inconsistent findings regarding the effect of glucose on Bdnf gene expression in microglial cell lines may be explained by the difference in the experimental design between the two studies.…”

HDAC4 Regulates Skeletal Muscle Regeneration via Soluble Factors

“…HDACs have been shown to regulate soluble factors in different cell types. In neuronal and glial cells, the release of brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 1 (FGF1) is mediated by HDACs ( Hossain et al, 2018 ), as well as in fibroblasts the production of several proinflammatory cytokines/chemokines ( Li et al, 2011 ), thus contributing to chronic inflammatory processes. Moreover, HDACs modulate IL-4 expression and secretion in mast cells and monocyte-derived DCs (moDCs) ( López-Bravo et al, 2013 ; Nakamaru et al, 2015 ).…”