TY - JOUR
T1 - Codonopsis pilosula polysaccharide attenuates tau hyperphosphorylation and cognitive impairments in htau infected mice
AU - Zhang, Qing
AU - Xia, Yiyuan
AU - Luo, Hongbin
AU - Huang, Sheng
AU - Wang, Yongjun
AU - Shentu, Yangping
AU - Mahaman, Yacoubou Abdoul Razak
AU - Huang, Fang
AU - Ke, Dan
AU - Wang, Qun
AU - Liu, Rong
AU - Wang, Jian Zhi
AU - Zhang, Bin
AU - Wang, Xiaochuan
N1 - Publisher Copyright:
© 2018 Zhang, Xia, Luo, Huang, Wang, Shentu, Mahaman, Huang, Ke, Wang, Liu, Wang, Zhang and Wang.
PY - 2018/11/27
Y1 - 2018/11/27
N2 - Codonopsis pilosula polysaccharide (CPPs), a natural products with potentially lower toxicity and better bioavailability has been used in traditional Chinese medicine for 1000s of years and a neuroprotective polysaccharide mitigates tau pathology in Alzheimer’s disease (AD) mouse model. However, whether CPPs can relieve AD pathology and cognitive defects remains poorly understood. Here we reported that CPPs remarkably increased the cell viability and PP2A activity, decreased tau phosphorylation in HEK 293/tau cells. Next, we employed an adeno-associated virus serotype 2 (AAV2)-induced expression of human full length tau (hTau) in C57/BL6 mice to mimic AD tau pathology. One month intragastric administration of CPPs significantly increased PP2A activity and reduced tau phosphorylation at Ser199, Ser202/Thr205 (AT8) and Thr231 in hippocampus of AAV2-hTau infected mice. Furthermore, behavioral tests revealed that CPPs rescued hTau overexpression induced cognitive defects while CPPs significantly increased the fEPSP slope and synaptic proteins including synaptotagmin and synaptophysin. Together, our data suggest that CPPs might prevent AD-like tau hyperphosphorylation via activation of PP2A and attenuates AD-like cognitive impairments through restoring the synaptic plasticity and synaptogenesis. In conclusion, our findings suggest that CPPs might be a potential candidate compound for the treatment of tau related diseases.
AB - Codonopsis pilosula polysaccharide (CPPs), a natural products with potentially lower toxicity and better bioavailability has been used in traditional Chinese medicine for 1000s of years and a neuroprotective polysaccharide mitigates tau pathology in Alzheimer’s disease (AD) mouse model. However, whether CPPs can relieve AD pathology and cognitive defects remains poorly understood. Here we reported that CPPs remarkably increased the cell viability and PP2A activity, decreased tau phosphorylation in HEK 293/tau cells. Next, we employed an adeno-associated virus serotype 2 (AAV2)-induced expression of human full length tau (hTau) in C57/BL6 mice to mimic AD tau pathology. One month intragastric administration of CPPs significantly increased PP2A activity and reduced tau phosphorylation at Ser199, Ser202/Thr205 (AT8) and Thr231 in hippocampus of AAV2-hTau infected mice. Furthermore, behavioral tests revealed that CPPs rescued hTau overexpression induced cognitive defects while CPPs significantly increased the fEPSP slope and synaptic proteins including synaptotagmin and synaptophysin. Together, our data suggest that CPPs might prevent AD-like tau hyperphosphorylation via activation of PP2A and attenuates AD-like cognitive impairments through restoring the synaptic plasticity and synaptogenesis. In conclusion, our findings suggest that CPPs might be a potential candidate compound for the treatment of tau related diseases.
KW - Alzheimer’s disease
KW - Codonopsis pilosula polysaccharide
KW - Cognitive impairment
KW - PP2A
KW - Tau
UR - http://www.scopus.com/inward/record.url?scp=85058986210&partnerID=8YFLogxK
U2 - 10.3389/fnmol.2018.00437
DO - 10.3389/fnmol.2018.00437
M3 - Article
AN - SCOPUS:85058986210
SN - 1662-5099
VL - 11
JO - Frontiers in Molecular Neuroscience
JF - Frontiers in Molecular Neuroscience
M1 - 437
ER -