Pseudoginsenoside-F11 ameliorates okadiac acid-induced learning and memory impairment in rats via modulating protein phosphatase 2A. (July 2021)

• Record Type: Journal Article
• Authors: Chu, Jinxiu; Wang, Jian; Cui, Lijuan; Liu, Shuai; An, Nina; Han, Jian; Che, Xiaohang; Wu, Chunfu; Yang, Jingyu
• Is Part Of: Mechanisms of ageing and development. Volume 197(2021)
• Publication Date: 2021-07
• Subjects: AD Alzheimer's disease -- PF11 pseudoginsenoside-F11 -- OA okadaic acid -- PP2A protein phosphatase 2A -- Aβ β-amyloid -- APP amyloid precursor protein -- GSK-3β glycogen synthase kinase-3 beta -- LCMT leucine carboxyl methyltransferase -- PME protein phosphatase methylesterase -- SLA spontaneous locomotor activity -- NOR novel object recognition -- MWM Morris water maze -- ELISA enzyme-linked immunosorbent assay -- PBS phosphate buffered solution -- TEM transmission electron microscope -- WB western blotting -- SYN synaptophysin -- PSD95 postsynaptic density 95; Alzheimer's disease -- Pseudoginsenoside-F11 -- Okadaic acid -- Tau hyperphosphorylation -- Protein phosphatase 2A; Aging -- Periodicals; Developmental biology -- Periodicals; Aging -- Periodicals; Developmental Biology -- Periodicals; Vieillissement -- Périodiques; Biologie du développement -- Périodiques; Aging; Developmental biology; Periodicals; 612.67
• DOI: 10.1016/j.mad.2021.111496
• Languages: English
• ISSNs: 0047-6374

Abstract

Graphical abstract: Highlights: Pseudoginsenoside-F11 significantly improved the self-care ability of the rats and ameliorated okadiac acid-induced learning and memory impairment in rats. Pseudoginsenoside-F11 significantly rescued okadiac acid-induced neuronal death and synaptic damage in rats. Pseudoginsenoside-F11 significantly alleviated okadiac acid-induced neuroinflammation in rats. Pseudoginsenoside-F11 significantly reversed okadiac acid-induced tau hyperphosphorylation in rats. Pseudoginsenoside-F11 significantly increased the activity of protein phosphatase 2A in vivo and in vitro . Abstract: We have reported that pseudoginsenoside-F11 (PF11) can significantly improve the cognitive impairments in several Alzheimer's disease (AD) models, but the mechanism has not been fully elucidated. In the present study, the effects of PF11 on AD, in particular the underlying mechanisms related with protein phosphatase 2A (PP2A), were investigated in a rat model induced by okadaic acid (OA), a selective inhibitor of PP2A. The results showed that PF11 treatment dose-dependently improved the learning and memory impairments in OA-induced AD rats. PF11 could significantly inhibit OA-induced tau hyperphosphorylation, suppress the activation of glial cells, alleviate neuroinflammation, thus rescue the neuronal and synaptic damage. Further investigation revealed that PF11 could regulate the protein expression of methyl modifying enzymes (leucine carboxyl methyltransferase-1 and protein phosphatase methylesterase-1) in the brain, thus increase methyl-PP2A protein expression and indirectly increase the activity of PP2A. Molecular docking analysis, structural alignment and in vitro results showed that PF11 was similar in the shape and electrostatic field feature to a known activator of PP2A, and could directly bind and activate PP2A. In conclusion, the present data indicate that PF11 can ameliorate OA-induced learning and memory impairment in rats via modulating PP2A.