黄芪甲苷通过影响NogoA/NgR 和cAMP/PKA 通路改善APP/PS1 转基因小鼠认知功能.

AIM: To investigate the effect of astragaloside IV （AST IV） on cognition and pathology in Alzheimer disease （AD） mouse model, and to explore its underlying possible mechanism. METHODS: The APP/PS1 transgenic mice were randomly classified into AD+AST IV and AD groups, and C57BL/6 wild-type （WT） mice were used as control group（ WT group）. The mice were treated by intragastric administration for 2 months. Morris water maze and Ymaze tests were performed to evaluate the spatial cognitive function of the mice. Nissl staining was used to detect the number and morphology of neurons, while immunofluorescence staining was used to detect neuronal nuclear antigen （NeuN） and amyloid β-protein （Aβ） levels. The expression levels of neurite outgrowth inhibitor A （NogoA）, Nogo-66 receptor （NgR）, p75 neurotrophin receptor （p75NTR）, leucine rich repeat and immunoglobin-like domain-containing protein-1 （LINGO-1）, cyclic adenosine monophosphate （cAMP）, and protein kinase A （PKA） in the whole brain were detected by Western blot. RESULTS: Treatment with AST IV significantly improved cognitive function in APP/PS1 mice, and enhanced learning, memory and exploration abilities. Compared with WT mice, APP/PS1 mice exhibited increased Aβ deposition in the cerebral cortex and hippocampus （P<0. 01）, significant loss of Nissl bodies （P<0. 05 or P<0. 01）, and decreased number of neurons （P<0. 05）. However, AST IV treatment significantly reduced Aβ deposition （P<0. 05） and the loss of Nissl bodies（ P<0. 05）, and increased the number of neurons（ P<0. 05）. Compared with WT mice, the expression levels of NogoA, NgR, p75NTR and LINGO-1 in the whole brain tissue of APP/PS1 mice were significantly increased （P<0. 05 or P<0. 01）, whereas those of cAMP and PKA were significantly decreased （P<0. 05 or P<0. 01）. However, AST IV treatment significantly inhibited the expression of NogoA, NgR, p75NTR and LINGO-1 （P<0. 05 or P<0. 01）, and increased the expression of cAMP and PKA（ P<0. 05）. CONCLUSION: Treatment with AST IV reduced Aβ deposition and neuronal damage in the brains of APP/PS1 mice by inhibiting the expression of NogoA and NgR/p75NTR/LINGO-1 receptor complex and up-regulating the cAMP/PKA signaling pathway. [ABSTRACT FROM AUTHOR]