Department of Neuroinflammation and Brain Fatigue Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Mol Neurobiol. 2018 Apr;55(4):3408-3425. doi: 10.1007/s12035-017-0578-3. Epub 2017 May 13.
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.
葡萄糖被认为可以改善人类和老鼠的记忆力，但详细的机制仍不清楚。在这项研究中，我们专注于两种主要的神经营养因子，脑源性神经营养因子（BDNF）和成纤维细胞生长因子 1（FGF1），它们被认为与记忆增强有关，并评估了它们在小鼠神经元和神经胶质细胞中的表达调控。我们的研究结果表明，葡萄糖给药可增加磷酸化 Akt、磷酸化 CREB、外显子 1 和外显子 4 特异性 BDNF 转录本，以及与预期打开染色质和减少组蛋白去乙酰化酶 2（HDAC2）相关的 FGF1 转录本，在小鼠海马神经元和星形胶质细胞中。葡萄糖给药增强了 CA1 和 CA3 海马区的长时程增强和树突棘数量。海马内注射短发夹 RNA 针对 TrkB 可消除葡萄糖介导的记忆增强。与葡萄糖一样，我们还报告说，HDAC 抑制剂可以通过 BDNF-TrkB 途径增强记忆，但它针对不同的脑细胞群来增强 BDNF 和 FGF1 转录本。此外，可溶性 FGF1 处理可显著增加星形胶质细胞和神经元中的 BDNF 表达，表明葡萄糖介导的神经营养因子诱导可能有助于记忆。我们的研究提供了有价值的见解，解释了葡萄糖和 HDAC 抑制剂对神经营养因子的独特神经元和神经胶质细胞调控，这可能解释了我们的脑细胞如何控制神经营养因子的释放。
