The Study On Curcumin Prevents Cisplatin-Induced Cognitive Impairment By Promoting Autophagy

Cognitive impairment caused by cisplatin chemotherapy still deeply afflicts patients after many years of chemotherapy,and has a serious adverse effect on their work and study and quality of life.The purpose of this study was to investigate whether curcumin can improve the cognitive impairment caused by cisplatin,and to elucidate whether the effects were related to autophagy or apoptosis.It provides a new solution to the clinical treatment of cognitive impairment caused by cisplatin.In this study,the research content was divided into two parts according to the purpose of the experiment: the first part is the effect of curcumin on cisplatin-induced cognitive impairment and its mechanism,and the second part is the effect of curcumin on improving cognitive impairment after intervention with autophagy inhibitor 3-MA.We established a cisplatin-induced cognitive impairment model by intraperitoneal injection of cisplatin(2.3 mg/kg)in mice,while curcumin was orally administered at 100 mg/kg and intervention with autophagy inhibitor 3-MA.The effect of curcumin on the number of autophagosomes in hippocampus of mice was observed by transmission electron microscopy.The expression levels of autophagy marker proteins and apoptosis-related proteins in hippocampus of mice were detected by Western Blot,and the expression levels of inflammatory factors were detected by qRT-PCR.Finally,immunofluorescence and Golgi staining experiments were performed to detect the number of new neurons and synaptic spines.In the first part of the study,firstly,the results of the open-field test showed that curcumin could significantly increase the number of crossing grids and the number of rearing in cognitively impaired mice;the results of novel object recognition test showed that curcumin could significantly increase the cognitive index in cognitively impaired mice;Morris water maze test showed that curcumin could significantly increase the number of crossings and significantly shorten the escape latency.The above experimental results indicate that curcumin can improve the spontaneous activity behavior,inquiry behavior,ability of learning and memory of the shape and size of new object,and spatial memory ability in mice induced by cisplatin.Secondly,transmission electron microscopy showed that curcumin significantly reduced the number of cisplatin-induced autophagosomes;Western Blot and immunofluorescence experiments showed that curcumin significantly increased the expression of LC3 II and inhibited the expression of P62,indicating that the cisplatin-induced autophagy pathway is further activated by curcumin.Then,Western Blot showed that curcumin significantly increased the expression of anti-apoptotic protein Bcl-2 and inhibited the expression of proapoptotic proteins Bax and Bim,that is to say,curcumin inhibited the apoptosis process.Finally,qRT-PCR experiments showed that curcumin had no significant effect on the expression of inflammatory factors IL-1beta,IL-6 and TNF-alpha;immunofluorescence experiments showed that curcumin could significantly increase the number of new neurons,but had no significant effect on the number of microglia;Golgi staining showed that curcumin treatment significantly increased the number of synaptic spines in the hippocampus of mice.The above results indicate that curcumin has neuroprotective effects which is not related to inflammatory.In the second part of the study,after intervention of autophagy inhibitor 3-MA,first,transmission electron microscopy showed that 3-MA inhibited the increase in the number of autophagosomes induced by curcumin and cisplatin.The results of Western Blot experiments and immunofluorescence experiments showed that 3-MA inhibited the expression of cisplatin-induced LC3 II and increased the expression of P62.The above results indicated that 3-MA inhibited curcumin and cisplatin-induced autophagy.Then,Western blotting results showed that 3-MA inhibited the anti-apoptotic protein Bcl-2 and increased the expression of the pro-apoptotic proteins Bax and Bim,indicating that 3-MA promoted apoptosis.Finally,immunofluorescence results showed that 3-MA increased the number of neonatal neurons in the hippocampal DG region of cisplatin-induced mice,indicating that 3-MA improved cognitive impairment caused by cisplatin.In conclusion,curcumin exerts neuroprotective effects by inducing autophagy,and the achievement of this result may involve maintaining the autophagy/apoptosis balance process.In addition,curcumin improves cognitive impairment independent of neuroinflammatory.