Influence of sevoflurane exposure on mitogen-activated protein kinases and Akt/GSK-3β/CRMP-2 signaling pathways in the developing rat brain

  • Authors:
    • Yafang Liu
    • Chuiliang Liu
    • Minting Zeng
    • Xue Han
    • Kun Zhang
    • Yanni Fu
    • Jue Li
    • Yujuan Li
  • View Affiliations

  • Published online on: December 18, 2017     https://doi.org/10.3892/etm.2017.5651
  • Pages: 2066-2073
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Abstract

Prolonged exposure to volatile anesthetics causes neurodegeneration in developing animal brains. However, their underlying mechanisms of action remain unclear. The current study investigated the expression of proteins associated with the mitogen‑activated protein kinases (MAPK) and protein kinase B (Akt)/glycogen synthase kinase‑3β (GSK‑3β)/collapsin response mediator protein 2 (CRMP‑2) signaling pathways in the cortices of neonatal mice following exposure to sevoflurane. Seven‑day‑old (P7) neonatal C57BL/6 mice were randomly divided into 2 groups and either exposed to 2.6% sevoflurane or air for 6 h. Terminal deoxyribonucleotide transferase mediated dUTP nick end labeling (TUNEL) staining, as well as the expression of activated caspase‑3 and α‑fodrin, was used to detect neuronal apoptosis in the cortices of mice. MAPK signaling pathways were investigated by detecting the expression of phosphorylated (p‑) extracellular signal‑regulated kinase 1/2 (ERK1/2), p‑cyclic adenosine monophosphate response element‑binding protein (CREB), p‑p38, p‑nuclear factor (NF‑κB) and p‑c‑Jun N‑terminal kinase (p‑JNK). Akt/GSK‑3β/CRMP‑2 signaling pathways were assessed by detecting the expression of p‑Akt, p‑GSK‑3β and p‑CRMP‑2 in the cortices of P7 mice 2 h following exposure to sevoflurane. The results demonstrated that sevoflurane significantly increased the apoptosis of cells in the retrosplenial cortex (RS), frontal cortex (FC) and parietal association cortex (PtA), increased the expression of cleaved caspase‑3 expression and promoted the formation of 145 kDa and 120 kDa fragments from α‑fodrin. Sevoflurane inhibited the phosphorylation of ERK1/2 and CREB, stimulated the phosphorylation of p38 and NF‑κB, but did not significantly affect the phosphorylation of JNK. Furthermore, sevoflurane inhibited the phosphorylation of Akt, decreased the phosphorylation of GSK‑3β at ser9 and increased the phosphorylation of CRMP2 at Thr514. These results suggest that multiple signaling pathways, including ERK1/2, P38 and Akt/GSK‑3β/CRMP‑2 may be involved in sevoflurane‑induced neuroapoptosis in the developing brain.

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February-2018
Volume 15 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Liu Y, Liu C, Zeng M, Han X, Zhang K, Fu Y, Li J and Li Y: Influence of sevoflurane exposure on mitogen-activated protein kinases and Akt/GSK-3β/CRMP-2 signaling pathways in the developing rat brain. Exp Ther Med 15: 2066-2073, 2018.
APA
Liu, Y., Liu, C., Zeng, M., Han, X., Zhang, K., Fu, Y. ... Li, Y. (2018). Influence of sevoflurane exposure on mitogen-activated protein kinases and Akt/GSK-3β/CRMP-2 signaling pathways in the developing rat brain. Experimental and Therapeutic Medicine, 15, 2066-2073. https://doi.org/10.3892/etm.2017.5651
MLA
Liu, Y., Liu, C., Zeng, M., Han, X., Zhang, K., Fu, Y., Li, J., Li, Y."Influence of sevoflurane exposure on mitogen-activated protein kinases and Akt/GSK-3β/CRMP-2 signaling pathways in the developing rat brain". Experimental and Therapeutic Medicine 15.2 (2018): 2066-2073.
Chicago
Liu, Y., Liu, C., Zeng, M., Han, X., Zhang, K., Fu, Y., Li, J., Li, Y."Influence of sevoflurane exposure on mitogen-activated protein kinases and Akt/GSK-3β/CRMP-2 signaling pathways in the developing rat brain". Experimental and Therapeutic Medicine 15, no. 2 (2018): 2066-2073. https://doi.org/10.3892/etm.2017.5651