Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan.
Molecules. 2020 Aug 12;25(16):3667. doi: 10.3390/molecules25163667.
Brain-derived neurotrophic factor (BDNF) is an important factor for memory consolidation and cognitive function. Protein kinase A (PKA) signaling interacts significantly with BDNF-provoked downstream signaling. Glucosamine (GLN), a common dietary supplement, has been demonstrated to perform a variety of beneficial physiological functions. In the current study, an in vivo model of 7-week-old C57BL/6 mice receiving daily intraperitoneal injection of GLN (0, 3, 10 and 30 mg/animal) was subjected to the novel object recognition test in order to determine cognitive performance. GLN significantly increased cognitive function. In the hippocampus GLN elevated tissue cAMP concentrations and CREB phosphorylation, and upregulated the expression of BDNF, CREB5 and the BDNF receptor TrkB, but it reduced PDE4B expression. With the in vitro model in the HT22 hippocampal cell line, GLN exposure significantly increased protein and mRNA levels of BDNF and CREB5 and induced cAMP responsive element (CRE) reporter activity; the GLN-mediated BDNF expression and CRE reporter induction were suppressed by PKA inhibitor H89. Our current findings suggest that GLN can exert a cognition-enhancing function and this may act at least in part by upregulating the BDNF levels via a cAMP/PKA/CREB-dependent pathway.
脑源性神经营养因子（BDNF）是记忆巩固和认知功能的重要因素。蛋白激酶 A（PKA）信号与 BDNF 引发的下游信号显著相互作用。葡萄糖胺（GLN）是一种常见的膳食补充剂，已被证明具有多种有益的生理功能。在本研究中，对接受每日腹腔注射 GLN（0、3、10 和 30 mg/动物）的 7 周龄 C57BL/6 小鼠进行体内模型，进行新物体识别测试以确定认知表现。GLN 显著提高了认知功能。在海马体中，GLN 升高了组织 cAMP 浓度和 CREB 磷酸化水平，并上调了 BDNF、CREB5 和 BDNF 受体 TrkB 的表达，但降低了 PDE4B 的表达。在 HT22 海马细胞系的体外模型中，GLN 暴露显著增加了 BDNF 和 CREB5 的蛋白和 mRNA 水平，并诱导 cAMP 反应元件（CRE）报告基因活性；PKA 抑制剂 H89 抑制了 GLN 介导的 BDNF 表达和 CRE 报告基因诱导。我们目前的研究结果表明，GLN 可以发挥增强认知的作用，这至少部分是通过 cAMP/PKA/CREB 依赖性途径上调 BDNF 水平来实现的。
