Study on myelin injury of AD mice treated with Shenzhiling oral liquid in the PI3K/Akt–mTOR pathway

Abstract

Shenzhiling oral liquid (SZL) is a Traditional Chinese Medicine (TCM) compound to be approved by the China Food and Drug Administration (CFDA) (Z20120010) for the treatment of mild-to-moderate Alzheimer's disease (AD). However, its mechanism in early AD is not clear. We studied its mechanism in protecting myelin. Three-month-old APPswe/PS1dE9double transgenic mice were used as AD model and wild-type C57BL/6 mice were used as control. After 3-month intervention, the Morris water maze was used to detect behavioural changes. Myelin mTOR pathway (PI3K, p-PI3K, Akt, p-Akt, mTOR, p-mTOR), myelin basic protein (MBP) and postsynaptic density protein 95 (PSD95) were detected by immunohistochemistry and western blot and reverse transcriptase polymerase chain reaction (RT-PCR). After 3 months of SZL treatment, compared with the model group (M), SZL medium-dose (SM) and SZL low-dose groups (SL) exhibited increased staying and crossing results in Morris water maze (<i>P</i> < 0.05). Compared with M, PI3K-positive cells in SM and SL groups were increased (<i>P</i> < 0.01), p-PI3K expression increased in the Donepezil group (D), SZL high-dose group (SH) and SM (<i>P</i> < 0.05); number of Akt-positive cells and Akt expression in D, SM and SL were increased (<i>P</i> < 0.01, <i>P</i> < 0.05); number of p-Akt- and mTOR-positive cells and mTOR expression in all drug-treated groups were significantly increased (<i>P</i> < 0.01); p-Akt and p-mTOR expression increased in all drug-treated groups (<i>P</i> < 0.05, <i>P</i> < 0.01); MBP expression in D and SH increased (<i>P</i> < 0.05), while in SM and SL it increased more significantly (<i>P</i> < 0.01); and PSD95 expression in D, SM and SL was increased (<i>P</i> < 0.05). RT-PCR results showed that compared with M, PI3K mRNA and Akt mRNA expression in all drug-treated groups increased, but there was no statistical difference (<i>P</i> > 0.05), mTOR mRNA expression in all the drug-treated groups increased significantly (<i>P</i> < 0.01) and MBP mRNA and PSD95 mRNA expression in D and SH increased (<i>P</i> < 0.05). SZL oral liquid could play a role in myelin protection in early AD.