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

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Summary

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.

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Authors and Affiliations

  1. Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China

    Deng-lei Ma, Yi Luo, Rui Huang, Li Zhang, Ya-li Li, Lin Li & Lan Zhang

  2. Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China

    Deng-lei Ma, Yi Luo, Rui Huang, Li Zhang, Ya-li Li, Lin Li & Lan Zhang

  3. Beijing Institute for Brain Disorders, Beijing, 100053, China

    Deng-lei Ma, Yi Luo, Rui Huang, Li Zhang, Ya-li Li, Lin Li & Lan Zhang

  4. Beijing Engineering Research Center for Nerve System Drugs, Beijing, 100053, China

    Deng-lei Ma, Yi Luo, Rui Huang, Li Zhang, Ya-li Li, Lin Li & Lan Zhang

  5. Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China

    Yi Luo & Qi Wang

  6. Renaissance School of Medicine at Stony Brook University, Stony Brook, New York, 11794, USA

    Zi-run Zhao

Authors
  1. Deng-lei Ma
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  2. Yi Luo
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  3. Rui Huang
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  4. Zi-run Zhao
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  5. Li Zhang
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  6. Ya-li Li
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  7. Qi Wang
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  8. Lin Li
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  9. Lan Zhang
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Corresponding authors

Correspondence to Lin Li or Lan Zhang.

Additional information

This research was supported by National Natural Science Foundation of China (Nos. 81473373, 81874351, 81673406), Capital Science and Technology Leading Talent Training Project (No. Z191100006119017), Beijing Hospitals Authority Ascent Plan (No. DFL20190803), and Cultivation Fund of Capital Medical University (No. PYZ19134).

Conflict of Interest Statement

The authors declare that there is no conflict of interest with any financial organization or corporation or individual that can inappropriately influence this work.

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Ma, Dl., Luo, Y., Huang, R. et al. Cornel Iridoid Glycoside Suppresses Hyperactivity Phenotype in rTg4510 Mice through Reducing Tau Pathology and Improving Synaptic Dysfunction. CURR MED SCI 40, 1031–1039 (2020). https://doi.org/10.1007/s11596-020-2284-z

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  • DOI: https://doi.org/10.1007/s11596-020-2284-z

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