Sevoflurane exposure in postnatal rats induced long-term cognitive impairment through upregulating caspase-3/cleaved-poly (ADP-ribose) polymerase pathway

Abstract

Abstract. The association of anesthetic exposure in infants or young children with the long-term impairment of neurologic functions has been reported previously; however, the underlying mechanisms remain largely unknown. In order to identify dysregulated gene expression underlying long-term cognitive impairment caused by sevoflurane exposure at the postnatal stage, the present study initially performed behavioral tests on adult Wistar rats, which received 3% sevoflurane at postnatal day 7 (P7) for different time course. Subsequently, transcriptome profiling of hippocampal tissues from experimental and control rats was performed. Significant impairment of the working memory was observed in adult rats with sevoflurane exposure for 4-6 h, when compared with the control rats. The results indicated that a total of 264 genes were aberrantly expressed (51 downregulated and 213 upregulated; fold change >2.0; P<0.05; false discovery rate <0.05) in the hippocampus of experimental adult rats compared with those from control rats. Particularly, the expression of caspase-3 gene (CASP3), encoding caspase-3 protein, presented the most significant upregulation, which was further validated by quantitative polymerase chain reaction and immunohistochemical analysis. Further analysis revealed that CASP3 expression level was negatively correlated with the rats' spatial working memory performance, as indicated by the Y-maze test. The level of cleaved-poly (ADP-ribose) polymerase (PARP), a substrate of caspase-3, was also increased in the hippocampus of experimental adult rats. Thus, the present study revealed that upregulation of caspase-3/cleaved-PARP may be involved in long-term cognitive impairment caused by sevoflurane exposure in infants, which may be useful for the clinical prevention of cognitive impairment.

Antiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron overload

“…Although we have not performed a direct measurement of apoptosis, increased cleaved PARP levels have been considered a marker of apoptosis because this protein is the substrate of activated caspases 43 . In agreement, upregulation of Caspase 3 gene expression in a model of cognitive impairment induced by sevoflurane was associated with increased cleaved PARP levels 44 . While Caspase 3 is an effector caspase, being part of the final common pathway of apoptosis, Cytochrome c, APAF 1, and Caspase 9 integrate the intrinsic apoptotic pathway.…”

α-bisabolol enhances radiotherapy-induced apoptosis in endometrial cancer cells by reducing the effect of XIAP on inhibiting caspase-3

“…It is shown that COX-2 was inhibited by caspase-3 after irradiation, and the inhibition of COX-2 could sensitize cancer cells to apoptosis [22,23]. RAPR is another important substrate of caspase-3, in which it is decomposed to an 85-kDa product, cRAPR, that can be identified as an apoptotic marker [24][25][26].…”

Lycium�barbarum polysaccharides attenuates the apoptosis of hippocampal neurons induced by sevoflurane

“…3% seveflurane was used to construct the injury model, the concentration of which was just higher than that commonly used in clinical application and was commonly used in researches too (6,26), The groups were named LBP100+SEV, LBP200+SEV, LBP400+SEV, LBP600+SEV groups, respectively, Cells treated with 3% sevoflurane gas alone were named SEV group, Cells treated with 400 µg/ml LBPs were named LBP400 group, and cells without any treatment were considered as Control group.…”