Identification of the protective effect of Polygonatum sibiricum polysaccharide on d-galactose-induced brain ageing in mice by the systematic characterization of a circular RNA-associated ceRNA network

CONTEXT: Polygonatum sibiricum polysaccharide (PSP), derived from Polygonatum sibiricum Delar. ex Redoute (Liliaceae), is known to be able to delay the ageing process. However, the specific mechanisms underlying these effects are not clear. OBJECTIVE: To investigate the mechanisms underlying the effects of PSP treatment on brain ageing by the application of transcriptomic analysis. MATERIALS AND METHODS: Forty Kunming mice were randomly divided into four groups (control, d-galactose, low-dose PSP, high-dose PSP). Mice were administered d-galactose (50 mg/kg, hypodermic injection) and PSP (200 or 400 mg/kg, intragastric administration) daily for 60 days. Behavioural responses were evaluated with the Morris water maze and the profiles of circRNA, miRNA, and mRNA, in the brains of experimental mice were investigated during the ageing process with and without PSP treatment. RESULTS: PSP improved cognitive function during brain ageing, as evidenced by a reduced escape latency time (p < 0.05) and an increase in the number of times mice crossed the platform (p < 0.05). A total of 37, 13, and 679, circRNAs, miRNAs, and mRNAs, respectively, were significantly altered by PSP treatment (as evidenced by a fold change ≥2 and p < 0.05). These dysregulated RNAs were closely associated with synaptic activity. PSP regulated regulate nine mRNAs (Slc6a5, Bean1, Ace, Samd4, Olfr679, Olfr372, Dhrs9, Tsc1, Slc12a6), three miRNAs (mmu-miR-5110, mmu-miR-449a-5p, mmu-miR-1981-5p), and two circRNAs (2:29227578|29248878 and 5:106632925|106666845) in the competing endogenous RNA (ceRNA) network. DISCUSSION AND CONCLUSIONS: Our analyses showed that multiple circRNAs, miRNAs, and mRNAs responded to PSP treatment in mice experiencing brain ageing.