Cornel Iridoid Glycoside Protects Against STAT1-Dependent Synapse and Memory Deficits by Increasing N-Methyl-D-aspartate Receptor Expression in a Tau Transgenic Mice
| Autor: | Zirun Zhao, Weipeng Wei, Denglei Ma, Kai-Wen Guo, Lan Zhang, Rui Huang, Li-Hong Gu, Lin Li |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Aging P301S transgenic mouse Cognitive Neuroscience Receptor expression Neurosciences. Biological psychiatry. Neuropsychiatry AMPA receptor Synapse 03 medical and health sciences 0302 clinical medicine medicine Janus kinase-2/STAT1 Chemistry tau accumulation medicine.disease Cell biology NMDAR 030104 developmental biology Synaptic plasticity NMDA receptor Tauopathy Signal transduction Alzheimer’s disease 030217 neurology & neurosurgery cornel iridoid glycoside RC321-571 |
| Zdroj: | Frontiers in Aging Neuroscience, Vol 13 (2021) |
| ISSN: | 1663-4365 |
| Popis: | P301S transgenic mice are an animal model of tauopathy and Alzheimer’s disease (AD), exhibiting tau pathology and synaptic dysfunction. Cornel iridoid glycoside (CIG) is an active ingredient extracted from Cornus officinalis, a traditional Chinese herb. In the present study, the purpose was to investigate the effects and mechanisms of CIG on tau pathology and synaptic dysfunction using P301S transgenic mice. The results showed that intragastric administration of CIG for 3.5 months improved cognitive impairments and the survival rate of P301S mice. Electrophysiological recordings and transmission electron microscopy study showed that CIG improved synaptic plasticity and increased the ultrastructure and number of synapse. Moreover, CIG increased the expression levels of N-methyl-D-aspartate receptors (NMDAR) subunits GluN1, GluN2A, and GluN2B, and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluA1. We inferred that the major mechanism of CIG involving in the regulation of synaptic dysfunctions was inhibiting the activation of Janus kinase-2 (JAK2)/signal transducer and activator of transcription 1 (STAT1) signaling pathway and alleviating STAT1-induced suppression of NMDAR expressions. Based on our findings, we thought CIG might be a promising candidate for the therapy of tauopathy such as AD. |
| Databáze: | OpenAIRE |
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