title: Xanthoceras sorbifolia extracts ameliorate dendritic spine deficiency and cognitive decline via upregulation of BDNF expression in a rat model of Alzheimer's disease.
abstract: Xanthoceras sorbifolia, a traditional Chinese folk medicine with anti-inflammatory effects, has been used for a long time in China, especially in the Inner Mongolian area for the treatment of rheumatism. Inflammation is one of the main causes of Alzheimer's disease (AD). AD is characterized by aggregation of amyloid β-peptide (Aβ) plaques, neurofibrillary tangle formation, synaptic dysfunction and neuronal loss. To investigate whether Xanthoceras sorbifolia extracts (XSE) improve cognition and protect dendritic spines, we performed behavioral tests to investigate learning and memory in an Aβ25-35-induced dementia animal model of AD as well as Golgi staining to observe dendritic spine formation in CA1 pyramidal neurons and western blots to test the expression levels of PSD95, BDNF and downstream signaling pathways. Our results indicated that oral treatment with XSE significantly reduced cognitive impairments in behavioral tests (passive avoidance test, novel object recognition test, Y-maze test and Morris water maze test). Golgi staining results revealed that XSE ameliorated dendritic spine density deficits in CA1 pyramidal neurons in the hippocampus. Western blot analysis suggested that XSE upregulated PSD95, which is the major scaffolding protein in synapses. BDNF levels and the ratio of p-TrkB/TrkB increased, and the expression of the RhoA, a member of the Rho-GTPase family, and its downstream target protein ROCK2 decreased in the dementia animal model following treatment with XSE. Therefore, the cognition-improving effects of XSE probably resulted from dendritic spine protection effects through regulation of BDNF signaling pathways.
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Yinjie
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Jikai
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Xu
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Song
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Tianyan
authors.initials: T
authors.lastname: Chi
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Ji
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China; Department of pharmacology, Shenyang medical colleges, Shenyang, 110034, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Jin
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Shimeng
authors.initials: S
authors.lastname: Qiu
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Yapeng
authors.initials: Y
authors.lastname: Hou
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zheng
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Traditional Chinese Material Medica, Shenyang pharmaceutical University, Shenyang, 110016, China; Key Laboratory of Structure-based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address: mengdl@163.com.
authors.forename: Dali
authors.initials: D
authors.lastname: Meng
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address: libozou@163.com.
authors.forename: Libo
authors.initials: L
authors.lastname: Zou
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D049229:Dendritic Spines / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage; D010936:Plant Extracts / Q000008:administration & dosage*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB; D029631:Sapindaceae; D015854:Up-Regulation / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D019208:Brain-Derived Neurotrophic Factor; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D010936:Plant Extracts; C074636:amyloid beta-protein (25-35); C000621230:Ntrk2 protein, rat; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; C580818:ROCK2 protein, rat; D054460:rho-Associated Kinases; C000621224:RhoA protein, rat; D020741:rho GTP-Binding Proteins
keywords: Alzheimer's disease; BDNF; Dendritic spine; Learning and memory; Xanthoceras sorbifolia