Cornel Iridoid Glycoside Suppresses Hyperactivity Phenotype in rTg4510 Mice through Reducing Tau Pathology and Improving Synaptic Dysfunction

rTg4510 mice are transgenic mice expressing P301L mutant tau and have been developed as an animal model of tauopathies including Alzheimer's disease (AD). Besides cognitive impairments, rTg4510 mice also show abnormal hyperactivity behavior. Cornel iridoid glycoside (CIG) is an active ingredient extracted from Cornus officinalis, a traditional Chinese herb. The purpose of the present study was to investigate the effects of CIG on the emotional disorders such as hyperactivity, and related mechanisms. The emotional hyperactivity was detected by locomotor activity test and Y maze test. Immunofluorescent and immunohistochemical analyses were conducted to measure neuron loss and phosphorylated tau. Western blotting was used to detect the expression of related proteins. The results showed that intragastric administration of CIG for 3 months decreased the hyperactivity phenotype, prevented neuronal loss, reduced tau hyperphosphorylation and aggregation in the amygdala of rTg4510 mice. Meanwhile, CIG alleviated the synaptic dysfunction by increasing the expression of N-methyl-D-aspartate receptors (NMDARs) subunits GluN1 and GluN2A and αamino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunits GluA1 and GluA2, and increased the level of phosphorylated Ca2+/calmodulin dependent protein kinase II α (p-CaMK IIα) in the brain of rTg4510 mice. In conclusion, CIG may have potential to treat the emotional disorders in tauopathies such as AD through reducing tau pathology and improving synaptic dysfunction.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:40

Enthalten in:

Current medical science - 40(2020), 6 vom: 11. Dez., Seite 1031-1039

Sprache:

Englisch

Beteiligte Personen:

Ma, Deng-Lei [VerfasserIn]
Luo, Yi [VerfasserIn]
Huang, Rui [VerfasserIn]
Zhao, Zi-Run [VerfasserIn]
Zhang, Li [VerfasserIn]
Li, Ya-Li [VerfasserIn]
Wang, Qi [VerfasserIn]
Li, Lin [VerfasserIn]
Zhang, Lan [VerfasserIn]

Links:

Volltext

Themen:

Alzheimer’s disease
Cornel iridoid glycoside
Gprin1 protein, mouse
Hyperactivity
Iridoid Glycosides
Journal Article
MAPT protein, human
N-methyl D-aspartate receptor subtype 2A
Nerve Tissue Proteins
Plant Extracts
RTg4510 mouse
Receptors, N-Methyl-D-Aspartate
Synaptic function
Tau Proteins
Tau phosphorylation
Tauopathy
VH92ICR8HX

Anmerkungen:

Date Completed 24.09.2021

Date Revised 24.09.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s11596-020-2284-z

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM319916146