Repeated exposure to sevoflurane in neonatal rats impairs cognition in adulthood via the PKA‑CREB‑BDNF signaling pathway

Zhao,Jili; Ren,Jinyu; Liu,Shuang; Gong,Yanan; Meng,Ping; Tan,Haitao; Chen,Yonggang

doi:10.3892/etm.2021.10877

Repeated exposure to sevoflurane in neonatal rats impairs cognition in adulthood via the PKA‑CREB‑BDNF signaling pathway

Authors:
- Jili Zhao
- Jinyu Ren
- Shuang Liu
- Yanan Gong
- Ping Meng
- Haitao Tan
- Yonggang Chen
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Affiliations: Department of Anesthesiology, Zhangqiu District Maternal and Child Health Care Hospital, Jinan, Shandong 250200, P.R. China, Department of Anesthesiology, The Third Hospital of Jinan, Jinan, Shandong 250032, P.R. China, Department of Operating Room, Zhangqiu District Maternal and Child Health Care Hospital, Jinan, Shandong 250200, P.R. China, Department of Cardiovascular Medicine, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China, Department of Burn and Plastic Surgery, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China, Department of Anesthesiology, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China, Department of Anesthesiology, People's Hospital of Gaomi, Gaomi, Shandong 261500, P.R. China
Published online on: October 13, 2021 https://doi.org/10.3892/etm.2021.10877
Article Number: 1442
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sevoflurane (Sev) anesthesia is widely used in pediatrics due to its low blood‑gas partition coefficient and lack of pungency. However, Sev treatment may lead to cognitive dysfunction in later life. The current study administered Sev to neonatal rats to investigate the effects of Sev treatment on cognitive performance in adulthood. In total, 6‑day‑old rats received 3% Sev for 2 h daily for 3 consecutive days. The cognitive function of rats in adulthood was evaluated in 56‑day‑old rats by Morris water maze test. The hippocampal neuron morphology was observed by Nissl staining. Hippocampal brain‑derived neurotrophic factor (BDNF) levels were measured by ELISA. The protein expression of protein kinase A (PKA), cAMP response element binding protein (CREB), phosphorylated‑CREB (p‑CREB) and BDNF in hippocampus were assessed by western blotting. The water maze results demonstrated that neonatal treatment with Sev resulted in a significant impairment of cognition in 56‑day‑old adult rats. Behavioral analysis revealed that Sev treatment increased latency to first pass the platform and decreased residence in target quadrants and across platform frequency compared with the control group in Morris water maze tests. Furthermore, compared with the control group, neonatal exposure to Sev reduced the number of neurons and the concentration of BDNF in the hippocampus, a brain region important for learning and memory. Additionally, Sev significantly decreased the expression of PKA, p‑CREB, BDNF and the p‑CREB/CREB ratio. Treatment with bucladesine, a selective PKA agonist, partially reversed the deleterious effects of Sev. In summary, the results indicated that PKA‑CREB‑BDNF signaling served an important role in the cognitive decline caused by neonatal exposure to Sev.

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