Dataset Information

?-Lipoic Acid Maintains Brain Glucose Metabolism via BDNF/TrkB/HIF-1? Signaling Pathway in P301S Mice.

ABSTRACT: The microtubule-associated protein tau is closely correlated with hypometabolism in Alzheimer's disease (AD). ?-lipoic acid (LA), which is a naturally occurring cofactor in mitochondrial, has been shown to have properties that can inhibit the tau pathology and neuronal damage in our previous research. However, if LA affects glucose metabolism when it reverses tau pathology remains unclear, especially concerning the potential mechanism. Therefore, we make a further study using the P301S mouse model (a tauopathy and AD mouse model which overexpressing fibrillary tau) to gain a clear idea of the aforementioned problems. Here, we found chronic LA administration significantly increased glucose availability by elevating glucose transporter 3 (GLUT3), GLUT4, vascular endothelial growth factor (VEGF) protein and mRNA level, and heme oxygenase-1 (HO-1) protein level in P301S mouse brains. Meanwhile, we found that LA also promoted glycolysis by directly upregulating hexokinase (HK) activity, indirectly by increasing proliferator-activated receptor gamma coactivator 1-alpha (PGC-1?) and DNA repair enzymes (OGG1/2 and MTH1). Further, we found the underlying mechanism of restored glucose metabolism might involve in the activation of brain-derived neurotrophic factor (BDNF)/tyrosine Kinase receptor B (TrkB)/hypoxia-inducible factor-1? (HIF-1?) signaling pathway by LA treatment.

SUBMITTER: Zhang YH

PROVIDER: S-EPMC7471806 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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α-Lipoic Acid Maintains Brain Glucose Metabolism <i>via</i> BDNF/TrkB/HIF-1α Signaling Pathway in P301S Mice.

Zhang Yan-Hui YH Yan Xin-Zhu XZ Xu Shuang-Feng SF Pang Zhong-Qiu ZQ Li Lin-Bo LB Yang Yang Y Fan Yong-Gang YG Wang Zhuo Z Yu Xin X Guo Chuang C Ao Qiang Q

Frontiers in aging neuroscience 20200821

The microtubule-associated protein tau is closely correlated with hypometabolism in Alzheimer's disease (AD). α-lipoic acid (LA), which is a naturally occurring cofactor in mitochondrial, has been shown to have properties that can inhibit the tau pathology and neuronal damage in our previous research. However, if LA affects glucose metabolism when it reverses tau pathology remains unclear, especially concerning the potential mechanism. Therefore, we make a further study using the P301S mouse mod ...[more]

PMID: 32973490

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Dataset Information

?-Lipoic Acid Maintains Brain Glucose Metabolism via BDNF/TrkB/HIF-1? Signaling Pathway in P301S Mice.

Publications

α-Lipoic Acid Maintains Brain Glucose Metabolism <i>via</i> BDNF/TrkB/HIF-1α Signaling Pathway in P301S Mice.

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