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

• Published in: Experimental and therapeutic medicine Vol. 14; no. 4; pp. 3824 - 3830
• Main Authors: Ling, Yunzhi, Li, Xiaohong, Yu, Li, Liang, Qisheng, Lin, Xuewu, Yang, Xiaodi, Wang, Hongtao, Zhang, Ye
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications UK Ltd 01.10.2017; D.A. Spandidos
• Subjects: Age; Anesthesia; Animal cognition; Apoptosis; Clinical medicine; Cognitive ability; Gene expression; Laboratory animals; Nervous system; Neurotoxicity; Rodents; Studies; long-term cognitive impairment; sevoflurane; cleaved-poly (ADP-ribose) polymerase; caspase-3
• ISSN: 1792-0981; 1792-1015
• DOI: 10.3892/etm.2017.5004

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 ( ), 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 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.