Eriodictyol improves cognitive function of 5×FAD mice by regulating Nogo-A/NgR/ROCK2 signaling pathway

doi:10.12307/2023.589

Chinese Journal of Tissue Engineering Research ›› 2023, Vol. 27 ›› Issue (32): 5097-5102.doi: 10.12307/2023.589

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Eriodictyol improves cognitive function of 5×FAD mice by regulating Nogo-A/NgR/ROCK2 signaling pathway

Li Mengdi1, 2, Li Na1, 2, Guo Minfang2, Meng Tao2, Yu Jingwen2, Li Yanbing1, 2, Ma Cungen1, 2, Yu Jiezhong1, 2, 3

1Research Center of Neurobiology/The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation for Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi Province, China; 2Institute of Brain Science, Shanxi Datong University, Datong 037009, Shanxi Province, China; 3Datong Fourth People’s Hospital, Datong 037009, Shanxi Province, China

Received:2022-08-30 Accepted:2022-10-19 Online:2023-11-18 Published:2023-03-22
Contact: Yu Jiezhong, MD, Professor, Doctoral supervisor, Research Center of Neurobiology/The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation for Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi Province, China; Institute of Brain Science, Shanxi Datong University, Datong 037009, Shanxi Province, China; Datong Fourth People’s Hospital, Datong 037009, Shanxi Province, China Ma Cungen, MD, Professor, Doctoral supervisor, Research Center of Neurobiology/The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation for Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi Province, China; Institute of Brain Science, Shanxi Datong University, Datong 037009, Shanxi Province, China
About author:Li Mengdi, Master candidate, Research Center of Neurobiology/The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation for Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi Province, China; Institute of Brain Science, Shanxi Datong University, Datong 037009, Shanxi Province, China Li Na, Master candidate, Research Center of Neurobiology/The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation for Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi Province, China; Institute of Brain Science, Shanxi Datong University, Datong 037009, Shanxi Province, China
Supported by:
Shanxi Province "Four Batches" Science and Technology for Medical Innovation Program in 2022, No. 2022XM33 (to YJZ); Shanxi Province Basic Research Program, No. 20210302123476 (to GMF); Medical Science and Technology Leading Team Project of Shanxi Provincial Health Care Commission, No. 2020TD05 (to MCG); Open Project of the Key Research Laboratory of Benefiting Qi for Acting Blood Circulation for Multiple Sclerosis of State Administration of Traditional Chinese Medicine, No. 2021-KF-21S (to JMD)

Abstract

Abstract: BACKGROUND: Numerous studies have shown that nerve growth inhibitory factor (Nogo-A) can activate Rho-associated coiled-coil kinase (ROCK) by binding to its downstream molecules, thereby exerting an inhibitory effect on nerve axon growth, which is closely related to the accumulation of β-amyloid protein in Alzheimer’s disease. Pre-laboratory work has demonstrated that eriodictyol improves cognitive dysfunction in 5×FAD mice, but its modulation of the Nogo-A/NgR/ROCK2 signaling pathway has not been clarified.
OBJECTIVE: To investigate the effect of eriodictyol on cognitive function in 5×FAD mice via the Nogo-A/NgR/ROCK2 signaling pathway.
METHODS: Male C57BL/6 mice, 8 months old, were randomized into wild group and wild triodictyol-treated group, while 8-month-old male 5×FAD mice were divided into model group and eriodictyol-treated group, with eight animals in each group. Starting from 33 weeks of age, the wild eriodictyol-treated group and the eriodictyol-treated group were injected intraperitoneally with 10 μL/g eriodictyol daily, and the wild and model groups were injected with the same volume of saline for 2 months. Behavioral assays such as Morris water maze and Y-maze tests were performed, and the expression of β-amyloid 1-42, Nogo-A, NgR, p75NTR, Lingo1, ROCK2, p-ROCK2 and other related target proteins in brain were detected by western blot and immunohistochemistry after testing.
RESULTS AND CONCLUSION: Behavioral assay results showed that the spatial memory ability and novelty exploration ability were decreased in the model group compared with the wild group and the wild eriodictyol-treated group, while these abilities were improved in the eriodictyol-treated group compared with the model group. Immunohistochemistry and western blot results showed that the expression of β-amyloid 1-42, Nogo-A and its receptors such as NgR, p75NTR and Lingo-1 were increased in the model group compared with the wild group and the wild eriodictyol-treated group, and were all down-regulated in the eriodictyol-treated group compared with the model group. The expression of Rho kinase-related proteins ROCK2 and p-ROCK2 was increased in the model group compared with the wild group and wild eriodictyol-treated group, but was down-regulated in the eriodictyol-treated group compared with the model group. These findings suggest that eriodictyol treatment ameliorates cognitive dysfunction in 5×FAD mice, which is associated with inhibition of the Nogo-A/NgR/ROCK2 signaling pathway.

Key words: Alzheimer’s disease, eriodictyol, 5×FAD moues, neuroprotection, cognitive function

CLC Number:

Li Mengdi, Li Na, Guo Minfang, Meng Tao, Yu Jingwen, Li Yanbing, Ma Cungen, Yu Jiezhong. Eriodictyol improves cognitive function of 5×FAD mice by regulating Nogo-A/NgR/ROCK2 signaling pathway[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(32): 5097-5102.

Figures/Tables 4

References

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Eriodictyol improves cognitive function of 5×FAD mice by regulating Nogo-A/NgR/ROCK2 signaling pathway

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