Fasudil ameliorates cognitive deficits, oxidative stress
and neuronal apoptosis via inhibiting ROCK/MAPK
and activating Nrf2 signalling pathways in APP/PS1 mice

Wenyue Wei; Yuyin Wang; Jing Zhang; Qingfang Gu; Xiaoqin Liu; Lijuan Song; Zhi Chai; Minfang Guo; Jiezhong Yu; Cungen Ma

doi:10.5114/fn.2021.105130

eISSN: 1509-572x
ISSN: 1641-4640

Folia Neuropathologica

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abstract:

Original paper

Fasudil ameliorates cognitive deficits, oxidative stress and neuronal apoptosis via inhibiting ROCK/MAPK and activating Nrf2 signalling pathways in APP/PS1 mice

Wenyue Wei

^{1, 2, 3}

,

Yuyin Wang

^{2, 3}

,

Jing Zhang

^{2, 3}

,

Qingfang Gu

³

,

Xiaoqin Liu

³

,

Lijuan Song

^{1, 2}

,

Zhi Chai

^{1, 2, 3}

,

Minfang Guo

³

,

Jiezhong Yu

^{1, 3, 4}

,

Cungen Ma

^{1, 2, 3}

Department of Neurology, First Affiliated Hospital, Shanxi Medical University, Taiyuan, P.R. China
2Research Center of Neurobiology, The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Jinzhong 030619, P.R. China
Institute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, Datong, P.R. China
Department of Neurology, Datong Fourth People’s Hospital, Datong, P.R. China

Folia Neuropathol 2021; 59 (1): 32-49

DOI: https://doi.org/10.5114/fn.2021.105130

Online publish date: 2021/03/31

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AMA

Wei W, Wang Y, Zhang J, et al. Fasudil ameliorates cognitive deficits, oxidative stress
and neuronal apoptosis via inhibiting ROCK/MAPK
and activating Nrf2 signalling pathways in APP/PS1 mice. Folia Neuropathologica. 2021;59(1):32-49. doi:10.5114/fn.2021.105130.

APA

Wei, W., Wang, Y., Zhang, J., Gu, Q., Liu, X.,  & Song, L. et al. (2021). Fasudil ameliorates cognitive deficits, oxidative stress
and neuronal apoptosis via inhibiting ROCK/MAPK
and activating Nrf2 signalling pathways in APP/PS1 mice. Folia Neuropathologica, 59(1), 32-49. https://doi.org/10.5114/fn.2021.105130

Chicago

Wei, Wenyue, Yuyin Wang, Jing Zhang, Qingfang Gu, Xiaoqin Liu, Lijuan Song,  and Zhi Chai et al. 2021. "Fasudil ameliorates cognitive deficits, oxidative stress
and neuronal apoptosis via inhibiting ROCK/MAPK
and activating Nrf2 signalling pathways in APP/PS1 mice". Folia Neuropathologica 59 (1): 32-49. doi:10.5114/fn.2021.105130.

Harvard

Wei, W., Wang, Y., Zhang, J., Gu, Q., Liu, X., Song, L., Chai, Z., Guo, M., Yu, J.,  and Ma, C. (2021). Fasudil ameliorates cognitive deficits, oxidative stress
and neuronal apoptosis via inhibiting ROCK/MAPK
and activating Nrf2 signalling pathways in APP/PS1 mice. Folia Neuropathologica, 59(1), pp.32-49. https://doi.org/10.5114/fn.2021.105130

MLA

Wei, Wenyue et al. "Fasudil ameliorates cognitive deficits, oxidative stress
and neuronal apoptosis via inhibiting ROCK/MAPK
and activating Nrf2 signalling pathways in APP/PS1 mice." Folia Neuropathologica, vol. 59, no. 1, 2021, pp. 32-49. doi:10.5114/fn.2021.105130.

Vancouver

Wei W, Wang Y, Zhang J, Gu Q, Liu X, Song L et al. Fasudil ameliorates cognitive deficits, oxidative stress
and neuronal apoptosis via inhibiting ROCK/MAPK
and activating Nrf2 signalling pathways in APP/PS1 mice. Folia Neuropathologica. 2021;59(1):32-49. doi:10.5114/fn.2021.105130.

PlumX metrics:

Alzheimer’s disease (AD) is a severe neurodegenerative disorder of the central nervous system (CNS) characterized by neuron loss and dementia. Previous abundant evidence demonstrates that the first critical step in the course of AD is the state of oxidative stress and the neuronal loss is closely related to the interaction of several signalling pathways. The neuroprotective efficacy of Rho-associated protein kinase (ROCK) inhibitor in the treatment of AD has been reported, but its exact mechanism has not been well elucidated. The purpose of this study is to investigate the therapeutic effects of Fasudil on amyloid precursor protein/presenilin-1 (APP/PS1) mice and to discover the potential underlying mechanism. Sixteen 8-month-old APP/PS1 mice were divided into model and Fasudil treatment groups and 8 wild-type mice were used as a normal control group. After the behavioural test, all mice were sacrificed for immunofluorescence and other biochemical tests. The results showed that the administration of Fasudil improved learning and memory ability, elevated the concentration of antioxidative substances and decreased lipid peroxides, as well as inhibited neuronal apoptosis by increasing the expression of B-cell lymphoma-2 (Bcl-2) (p < 0.05), reducing Bcl-2 Associated X (Bax) (p < 0.05) and cleaved caspase-3 (p < 0.05) of APP/PS1 mice. Moreover, Fasudil treatment also ameliorated the phosphorylation of p38 (p < 0.01), c-Jun N-terminal kinase (JNK) (p < 0.001) and extracellular regulated protein kinases (ERK) (p < 0.001), and accelerated the nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) (p < 0.01) expression and its antioxidative downstream molecules (p < 0.05, p < 0.05, and p < 0.05, respectively). Data from the present study demonstrate that Fasudil significantly restored cognitive function, restrained oxidative stress and reduced neuronal apoptosis in the hippocampus, probably by inhibiting ROCK/MAPK and activating Nrf2 signalling pathways in APP/PS1 mice.

keywords:

Fasudil ameliorates cognitive deficits, oxidative stress and neuronal apoptosis via inhibiting ROCK/MAPK and activating Nrf2 signalling pathways in APP/PS1 mice

Wenyue Wei 1, 2, 3 , Yuyin Wang 2, 3 , Jing Zhang 2, 3 , Qingfang Gu 3 , Xiaoqin Liu 3 , Lijuan Song 1, 2 , Zhi Chai 1, 2, 3 , Minfang Guo 3 , Jiezhong Yu 1, 3, 4 , Cungen Ma 1, 2, 3

Alzheimer’s disease, oxidative stress, apoptosis, ROCK, MAPK, Nrf2

Wenyue Wei

^{1, 2, 3}

,

Yuyin Wang

^{2, 3}

,

Jing Zhang

^{2, 3}

,

Qingfang Gu

³

,

Xiaoqin Liu

³

,

Lijuan Song

^{1, 2}

,

Zhi Chai

^{1, 2, 3}

,

Minfang Guo

³

,

Jiezhong Yu

^{1, 3, 4}

,

Cungen Ma

^{1, 2, 3}