Hai-Yang Yu1, Ye Zhu2, Xin-Li Zhang3, Lei Wang3, Yan-Meng Zhou3, Fang-Fang Zhang3, Han-Ting Zhang4, Xiao-Min Zhao5. 1. School of Pharmaceutical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai'an, 210046, People's Republic of China. yuhaiyang_15@163.com. 2. School of Radiology, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai'an, 210046, People's Republic of China. 3. School of Pharmaceutical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai'an, 210046, People's Republic of China. 4. School of Pharmacy, Qingdao University, Qingdao, 266073, People's Republic of China. 5. School of Chemistry and Pharmaceutical Engineering, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai'an, 210046, People's Republic of China.
Abstract
RATIONALE: Mitochondrial fragmentation contributes to the initiation of Alzheimer's disease (AD) pathology. Baicalin plays a significant role in rescuing mitochondrial dysfunction. However, the effect of baicalin treatment on the modulation of mitochondrial fragmentation has not yet been assessed. OBJECTIVES: The present study was designed to evaluate the effect of baicalin on memory and understand its mechanism of action. RESULTS: Baicalin treatment significantly reversed the altered learning and memory behaviours in AD mouse model. We found that baicalin treatment significantly improved the levels of microtubule association protein-2 and enhanced the expression of synaptophysin and postsynaptic density protein 95 (PSD95). Moreover, treatment with baicalin reversed amyloid-β oligomer (AβO)-induced abnormalities in the succinate dehydrogenase complex iron sulphur subunit B (SDHB) and cytochrome c oxidase components I (COXI) and mitochondrial fragmentation in the hippocampus. Further, we found that baicalin decreased the PDE4 levels and upregulated the levels of phosphorylated Ser157 site of vasodilator-stimulated phosphoprotein (pVASPs157) and phosphorylated Ser637 site of mitochondrial dynamin-related protein 1 (pDrp1S637). Moreover, in AβO-treated HT-22 cells, H89 inhibited the effect of baicalin on PSD95, mitochondrial fragmentation, SDHB and COXI, PDE4, pVASPs157, and pDrp1S637. CONCLUSION: The effect of baicalin on memory improvement may be due to improved synaptic plasticity, mitochondrial fragmentation, and rescue of dysfunction via the inhibition of PDE4, which leads to activation of pDrp1S637 in the AβO-induced model.
RATIONALE: Mitochondrial fragmentation contributes to the initiation of Alzheimer's disease (AD) pathology. Baicalin plays a significant role in rescuing mitochondrial dysfunction. However, the effect of baicalin treatment on the modulation of mitochondrial fragmentation has not yet been assessed. OBJECTIVES: The present study was designed to evaluate the effect of baicalin on memory and understand its mechanism of action. RESULTS: Baicalin treatment significantly reversed the altered learning and memory behaviours in AD mouse model. We found that baicalin treatment significantly improved the levels of microtubule association protein-2 and enhanced the expression of synaptophysin and postsynaptic density protein 95 (PSD95). Moreover, treatment with baicalin reversed amyloid-β oligomer (AβO)-induced abnormalities in the succinate dehydrogenase complex iron sulphur subunit B (SDHB) and cytochrome c oxidase components I (COXI) and mitochondrial fragmentation in the hippocampus. Further, we found that baicalin decreased the PDE4 levels and upregulated the levels of phosphorylated Ser157 site of vasodilator-stimulated phosphoprotein (pVASPs157) and phosphorylated Ser637 site of mitochondrial dynamin-related protein 1 (pDrp1S637). Moreover, in AβO-treated HT-22 cells, H89 inhibited the effect of baicalin on PSD95, mitochondrial fragmentation, SDHB and COXI, PDE4, pVASPs157, and pDrp1S637. CONCLUSION: The effect of baicalin on memory improvement may be due to improved synaptic plasticity, mitochondrial fragmentation, and rescue of dysfunction via the inhibition of PDE4, which leads to activation of pDrp1S637 in the AβO-induced model.
Authors: A M Bertholet; T Delerue; A M Millet; M F Moulis; C David; M Daloyau; L Arnauné-Pelloquin; N Davezac; V Mils; M C Miquel; M Rojo; P Belenguer Journal: Neurobiol Dis Date: 2015-10-19 Impact factor: 5.996
Authors: Jordano Brito-Moreira; Mychael V Lourenco; Mauricio M Oliveira; Felipe C Ribeiro; José Henrique Ledo; Luan P Diniz; Juliana F S Vital; Margaret H Magdesian; Helen M Melo; Fernanda Barros-Aragão; Jorge M de Souza; Soniza V Alves-Leon; Flavia C A Gomes; Julia R Clarke; Cláudia P Figueiredo; Fernanda G De Felice; Sergio T Ferreira Journal: J Biol Chem Date: 2017-03-10 Impact factor: 5.157