| BackgroundAlzheimer’s disease (AD) is an age-related neurodegenerative disease, which is caused by multiple factors and the mechanism is still not clear. There is nearly no way to reverse the neurodegenerative process, so treatments for AD patients are quite limited. Cattle encephalon glycoside and ignotin injection (CEGI) is a combination of mixed gangliosides, polypeptides, free amino acids, nucleic acids and total nitrogen, widely used in the treatment of central and peripheral nerve injuries in China for its effect of nerve repair, regeneration, nutrition and energy supplies. Given the multifactorial nature of AD, multitarget treatment is expected to improve AD. It is necessary to establish an AD animal model for investigating the etiology, mechanism and the drug of AD. For its single and shorter pathological changes, transgenic mouse model can better mimic the pathological characteristics and behavior changes of AD. It is rarely reported the effect of CEGI on AD with an APP/PS1 mouse model.In this study, we used CEGI administration in an APP/PS1 mouse model of AD to study the effect of CEGI for prevention and treatment on AD and provide evidences for further clinical experiment of CEGI.Materials and methodsAPP/PS1 mice were chosen as a AD model.12 non-transgenic C57 mice were used as normal control. Pre-test were divided into 5 groups, each group of 12, namely nTg group, Tg group, CEGI 6.6 mL/kg/day group, CEGI 13.2 mL/kg/day group, donepezil group. Formal test were divided into 7 groups, each group of 15, namely nTg group, Tg group, CEG 3.3 mL/kg/day group, CEGI 6.6 mL/kg/day group, CEGI 13.2 mL/kg/day group, donepezil group and CEGI/donepezil group. After 1 month of drug administration, the morris water maze test was performed. The morphology of neurons were detected by HE staining staining. SOD, MDA, CAT and GSH-PX levels in brain were measured by chemistry colorimetry. Insoluble A042, insoluble Aβ40, soluble Aβ42 and soluble Aβ40 levels and IL-10, TNF-a, IL-6 levels in brain and IL-10, TNF-a, IL-6 in serum were measured by ELISA. The expression of Aβ plaque, Bcl-2, Bax, NeuN and activated migcroglia were detected by immunohistochemical staining. Caspase-3 levels were measured by Western blot. The mRNA expression of bcl-2, bax, caspase-3, IL-10, TNF-a, IL-6 and IL-1β were measured by RT-PCR.Results1. CEGI treatment significantly shorten the mean escape latency and increased the time target quadrant of APP/PS1 mice.2. CEGI treatment significantly decreased Aβ palque burden and the cerebral insoluble Aβ42, insoluble Aβ40 and soluble Aβ42 levels of APP/PS1 mice.3. CEGI treatment increased the activities of SOD, GSH-PX and CAT and reduced the levels of MDA.4. CEGI attenuated neuronal damage and upregulated protein expression of NeuN, protein and mRNA expression of Bcl-2, the ratio of Bcl-2/Bax, and downregulated protein and mRNA expression of caspase-3 in the hippocampus of APP/PS1 mice.5. CEGI treatment significantly decreased the number of activated microglia and the level of TNF-a, IL-6 and the mRNA expression of TNF-a, IL-6, IL-1β in the cortex of the APP/PS1 mice and increased the levels of IL-10 in the brain and serum.Conclusion1. Administration of CEGI for 1 month significantly improved the spatial learning and memory deficits of APP/PS1 mice, making CEGI a promising therapeutic agent for AD.2. The opsitive effects of CEGI can be observed in 6.6mL/kg/day treatment group and CEGI/donepezil group.3. The beneficial effects of CEGI on APP/PS1 mice involve three aspects:(1) CEGI treatment significantly reduced Aβ plaque burden and insoluble and soluble Aβ levels in brains of APP/PS1 transgenic mice, and then decrease Aβ toxic damage in APP/PS1 transgenic mice.(2) CEGI treatment significantly increase the activity of antioxidases, decrease the products of lipid peroxidation, downregulate the expression of apoptotic genes and upregulate the expression of anti-apoptosis genes. These findings suggest CEGI could protect neurons in APP/PS1 mice, possibly by inhibiting oxidative stress and apoptosis of cells.(3) CEGI treatment could inhibit the activation of microglia, reduce the level of pro-inflammatory cytokines in brain and elevate the anti-inflammatory cytokines in brain and serum. These findings suggest CEGI could protect neurons in APP/PS1 mice, possibly by inhibiting inflammation response of cells. |
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