TGF-β1 Restores Hippocampal Synaptic Plasticity and Memory in Alzheimer Model via the PI3K/Akt/Wnt/β-Catenin Signaling Pathway.
Alzheimer's disease (AD) is the most common neurodegenerative disturbances. Dysfunction of synaptic plasticity and decline in cognitive functions are the most prominent features of AD, but the mechanisms of pathogenesis have not been well elucidated. In this paper, transforming growth factor-β1 (TGF-β1) was found to be reduced in the hippocampus of AD mouse which was accompanied by impaired pine density, synaptic plasticity, and memory function. Hippocampal injection of TGF-β1 rescued the AD-induced memory function impairment. In addition, TGF-β1 ameliorated synaptic plasticity and increased synaptic plasticity-associated protein expression including Arc, NR2B, and PSD-95 in mouse model of AD. Furthermore, we demonstrated that Akt/Wnt/β-catenin pathway protein expression in the hippocampus was suppressed in a mouse model of AD and TGF-β1 significantly enhanced the phosphorylation Akt, GSK3β, and increased the nuclear β-catenin. These results indicate that TGF-β1activates PI3K/Akt/Wnt/β-catenin signaling in mouse model of AD, which is important for promoting synaptic plasticity related to memory function. More importantly, suppression of PI3K/Akt/Wnt/β-catenin pathway compromised the beneficial effects of TGFβ1 in Alzheimer's model. Hence, TGF-β1 shows protective effect on neurons, which might be through the PI3K/Akt/Wnt/β-catenin signaling pathway, serving as a potential target in AD pathology.
['Hu|Yueqiang|Y|', 'Chen|Wei|W|', 'Wu|Lin|L|', 'Jiang|Lingfei|L|', 'Liang|Ni|N|', 'Tan|Lulu|L|', 'Liang|Minghui|M|', 'Tang|Nong|N|http://orcid.org/0000-0002-8852-3628']
D000544:Alzheimer Disease D000818:Animals D006624:Hippocampus D018782:Maze Learning D051379:Mice D009473:Neuronal Plasticity D019869:Phosphatidylinositol 3-Kinases D016212:Transforming Growth Factor beta D051153:Wnt Proteins D060449:Wnt Signaling Pathway D051176:beta Catenin
TGF-β1 PI3K/Akt/Wnt/β-catenin Cognitive functions Alzheimer’s disease