title: Oridonin Attenuates Synaptic Loss and Cognitive Deficits in an Aβ1-42-Induced Mouse Model of Alzheimer's Disease.
abstract: Synaptic loss induced by beta-amyloid (Aβ) plays a critical role in the pathophysiology of Alzheimer's disease (AD), but the mechanisms underlying this process remain unknown. In this study, we found that oridonin (Ori) rescued synaptic loss induced by Aβ1-42 in vivo and in vitro and attenuated the alterations in dendritic structure and spine density observed in the hippocampus of AD mice. In addition, Ori increased the expression of PSD-95 and synaptophysin and promoted mitochondrial activity in the synaptosomes of AD mice. Ori also activated the BDNF/TrkB/CREB signaling pathway in the hippocampus of AD mice. Furthermore, in the Morris water maze test, Ori reduced latency and searching distance and increased the number of platform crosses in AD mice. These data suggest that Ori might prevent synaptic loss and improve behavioral symptoms in Aβ1-42-induced AD mice.
authors.affiliation: Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China.
authors.forename: Sulei
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, PR China.
authors.forename: Linjie
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China.
authors.forename: Chaosheng
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Hui
authors.affiliation: Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China.|Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, PR China.|Jiangsu Stroke Research Collaborative Group, Nanjing, PR China.|Jiangsu Province Stroke Center for Diagnosis and Therapy, Nanjing, PR China.|Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, PR China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology*; D016229:Amyloid beta-Peptides; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000473:pathology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000076122:Disks Large Homolog 4 Protein; D045786:Diterpenes, Kaurane / Q000494:pharmacology / Q000627:therapeutic use*; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D000076122:Disks Large Homolog 4 Protein; D045786:Diterpenes, Kaurane; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D016708:Synaptophysin; C011959:oridonin; D020813:Receptor, trkB; D051528:Guanylate Kinases