RhoA/Rock2/Limk1/cofilin1 pathway is involved in attenuation of neuronal dendritic spine loss by paeonol in the frontal cortex of D‑galactose and aluminum‑induced Alzheimer’s disease‑like rat model

• Autorzy: Han F. , Xu H. , Shen J.-X. , Pan C. , Yu Z.-H. , Chen J.-J. , Zhu X.L. , Cai Y.-F. , Lu Y.-P.
• Języki publikacji: EN

Abstrakty

EN

Alzheimer’s disease (AD) has become the most prevalent neurodegenerative disorder. Given the pathogenesis of AD is unclear, there is currently no drug approved to halt or delay the progression of AD. Therefore, it is pressing to explore new targets and drugs for AD. In China, polyphenolic Chinese herbal medicine has been used for thousands of years in clinical application, and no toxic effects have been reported. In the present study, using D‑galactose and aluminum‑induced rat model, the effects of paeonol on AD were validated via the Morris water maze test, open field test, and elevated plus maze test. Neuronal morphology in frontal cortex was assessed using ImageJ’s Sholl plugin and RESCONSTRUCT software. RhoA/Rock2/Limk1/cofilin1 signaling pathway‑related molecules were determined by Western blotting. Cofilin1 and p‑cofilin1 were analyzed by immunofluorescence. Results showed that pre‑treatment with paeonol attenuated D‑galactose and aluminum‑induced behavioral dysfunction and AD‑like pathological alterations in the frontal cortex. Accompanied by these changes were the alterations in the dendrite and dendritic spine densities, especially the mushroom‑type and filopodia‑type spines in the apical dendrites, as well as actin filaments. In addition, the activity and intracellular distribution of cofilin1 and the molecules RhoA/Rock2/Limk1 that regulate the signaling pathway for cofilin1 phosphorylation have also changed. Our data suggests that paeonol may be through reducing Aβ levels to alleviate the loss of fibrillar actin and dendrites and dendritic spines via the Rho/Rock2/Limk1/cofilin1 signaling pathway in the frontal cortex, and ultimately improving AD‑like behavior.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2020
• Tom: 80
• Numer: 3
• Opis fizyczny: p.225-244,fig.,ref.

Twórcy

autor

Han F.

• College of Life Science, Anhui Normal University, Wuhu, China

autor

Xu H.

• College of Life Science, Anhui Normal University, Wuhu, China
• Anhui College of Traditional Chinese Medicine, Wuhu, China

autor

Shen J.-X.

• College of Life Science, Anhui Normal University, Wuhu, China

autor

Pan C.

• College of Life Science, Anhui Normal University, Wuhu, China

autor

Yu Z.-H.

• College of Life Science, Anhui Normal University, Wuhu, China

autor

Chen J.-J.

• College of Life Science, Anhui Normal University, Wuhu, China

autor

Zhu X.L.

• College of Life Science, Anhui Normal University, Wuhu, China
• Department of Anatomy, Wannan Medical College, Wuhu, China

autor

Cai Y.-F.

• College of Life Science, Anhui Normal University, Wuhu, China

autor

Lu Y.-P.

• College of Life Science, Anhui Normal University, Wuhu, China

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Identyfikatory

DOI

10.21307/ane‑2020‑021