Xanthoceraside modulates NR2B-containing NMDA receptors at synapses and rescues learning-memory deficits in APP/PS1 transgenic mice
Autor: | Lei Yang, Libo Zou, Xiaoli Guo, Peng Liu, Tianyan Chi, Danyang Liu, Lin Zhu, Xuemei Zhao, Xuefei Ji |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Dendritic spine Dendritic Spines Mice Transgenic Hippocampal formation Hippocampus Receptors N-Methyl-D-Aspartate Calcium in biology Synapse Amyloid beta-Protein Precursor Mice 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Memory Ca2+/calmodulin-dependent protein kinase Animals Learning Pharmacology Memory Disorders Amyloid beta-Peptides Neuronal Plasticity Chemistry musculoskeletal neural and ocular physiology Long-term potentiation Saponins Peptide Fragments Triterpenes Cell biology Disease Models Animal 030104 developmental biology nervous system Synapses Synaptic plasticity NMDA receptor Calcium-Calmodulin-Dependent Protein Kinase Type 2 030217 neurology & neurosurgery |
Zdroj: | Psychopharmacology. 235:337-349 |
ISSN: | 1432-2072 0033-3158 |
Popis: | Alzheimer’s disease (AD) is characterized by memory loss and synaptic damage. Previous studies suggested that xanthoceraside decreases glutamate-induced PC12 cell death, ameliorates memory deficits, and increases the number of dendritic spines in AD mice. These results indicated that xanthoceraside might have activities that protect synaptic plasticity. Herein, we detected the effect of xanthoceraside on synaptic function. Three-month-old APP/PS1 transgenic mice were orally treated with xanthoceraside (0.02, 0.08, or 0.32 mg/kg) once daily for 4 months and then behavioral tests were performed. LTP and Fluo-4/AM were carried out in vivo and in vitro, respectively. CaMKII-GluR1 and NR2B-associated proteins on synapses were measured. Xanthoceraside administration alleviated learning-memory deficits and increased the LTP in APP/PS1 transgenic mice. Meanwhile, xanthoceraside increased the expression of pT286-CaMKII in synaptic and extrasynaptic pools and CaMKII, pS831-GluR1, and GluR1 in synaptic pools. In addition, xanthoceraside increased the total pY1472-NR2B and NR2B expression and increased the levels of pY1472-NR2B in synaptic and extrasynaptic pools and NR2B in synaptic pools. However, NR2B was decreased in extrasynaptic pools, which might be associated with decreased expression of STEP61 and pY531-Fyn. In vitro studies showed that xanthoceraside inhibited intracellular calcium overload and increased the number of and extended the length of dendrites in primary hippocampal neurons compared with the Aβ25–35 group. The mechanism of xanthoceraside on ameliorating learning-memory deficits might be related to decrease intracellular calcium overload, increase CaMKII-GluR1 proteins, and up-regulate trafficking of pY1472-NR2B at synapse, thereby improving LTP in APP/PS1 transgenic mice. |
Databáze: | OpenAIRE |
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