Effects of penehyclidine hydrochloride on learning and memory in mice based on SIRT1/STAT3 pathway
Objective To investigate the effects of high-dose pentanethaquine hydrochloride(PHC)on learning and memory in mice and its mechanism.Methods Sixty C57BL/6J mice were divided into control group(intraperitoneal injection of 0.9％NaCl),experimental-L group(intraperitoneal injection of 0.12 mg·kg-1 PHC),experimental-H group(intraperitoneal injection of 5.00 mg·kg-1 PHC)and SRT1720 group[intraperitoneally injected 5.00 mg·kg-1 PHC and 5 mg·kg-1 silent information regulator 1(SIRT1)activator SRT1720],15 mice in each group.6 h after administration,learning and memory ability were tested by Morris water maze experiment or Y maze experiment.Western blot assay was used to detect the expression of SIRT1 and signal transducers and activators of transcription-3(STAT3)protein in mouse hippocampus;the levels of choline acetyl transferase(ChAT)in hippocampus of mice were detected by the kit;the expression of glial fibrillary acidic protein(GFAP)in hippocampus was detected by immunofluorescence.Results The times of crossing the platform in control group,experimental-L group,experimental-H group and SRT1720 group were 6.07±0.44,6.00±0.37,3.00±0.97 and 4.47±1.31;the escape latency periods were(14.02±1.79),(14.16±1.67),(51.55±4.07)and(32.84±2.40)s;Y maze alternating rate were(60.90±5.18)％,(59.38±5.99)％,(39.80±4.45)％and(46.65±5.02)％;SIRT1 protein expression levels were 1.05±0.09,1.08±0.12,0.52±0.07 and 0.77±0.11;the expression levels of STAT3 protein were 0.37±0.03,0.38±0.06,0.68±0.06 and 0.53±0.08;ChAT levels were(306.08±20.11),(296.33±36.11),(209.99±18.91)and(250.42±25.22)pg·mL-1;the average optical density of GFAP were 0.05±0.00,0.05±0.00,0.08±0.01 and 0.06±0.01.The above indexes of experimental-H group were compared with control group;the above indexes of experimental-H group were compared with experimental-L group;the above indexes of SRT1720 group were compared with experimental-H group;the differences were statistically significant(all P＜0.05).Conclusion High dose of PHC may decrease the learning and memory ability of mice by inhibiting SIRT1/STAT3 pathway.
pentanethaquine hydrochloridesilencing information regulatory factor 1/signal transduction and activator of transcription 3 signalslearning and memory ability
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