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Hippocampal mitogen-activated protein kinase activation is associated with intermittent hypoxia in a rat model of obstructive sleep apnea syndrome

  • Authors:
    • Ya‑Ning Zhao
    • Hong‑Yang Wang
    • Jian‑Min Li
    • Bao‑Yuan Chen
    • Guo Xia
    • Pan‑Pan Zhang
    • Yan‑Lei Ge

  • View Affiliations

  • Published online on: November 5, 2015     https://doi.org/10.3892/mmr.2015.4505
  • Pages: 137-145

  • Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Obstructive sleep apnea syndrome (OSAS), characterized by intermittent hypoxia/re‑oxygenation, may impair the cerebral system. Although mitogen‑activated protein kinase (MAPK) signaling was observed to have a key role in hypoxia‑induced brain injury, the intracellular events and their underlying mechanisms for intermittent hypoxia/re‑oxygenation-associated damage to hippocamal MAPKs, including extracellular signal‑regulated kinase (ERK)1/2, P38MAPK and c‑Jun N‑terminal kinase (JNK) remain to be elucidated and require further investigation. A total of five rats in each sub‑group were exposed to intermittent hypoxia or continued hypoxia for 2, 4, 6 or 8 weeks. Histological, immunohistochemical and biological analyses were performed to assess nerve cell injury in the hippocampus. Surviving CA1 pyramidal cells were identified by hematoxylin and eosin staining. The levels of phosphorylated ERK1/2, P38MAPK and JNK were detected by western blotting. B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax) in neural cells were examined by immunohistochemistry. The malondialdehyde (MDA) contents and superoxide dismutase (SOD) activities were measured by thiobarbituric acid and xanthine oxidation methods, respectively. Under continued hypoxia, the levels of phospho‑ERK1/2 peaked at the fourth week and then declined, whereas phospho‑P38MAPK and JNK were detected only in the late stages. By contrast, under intermittent hypoxia, ERK1/2, P38MAPK and JNK were activated at all time-points assessed (2, 4, 6 and 8 weeks). The levels of phospho‑ERK1/2, P38MAPK and JNK were all higher in the intermittent hypoxia groups than those in the corresponding continued hypoxia groups. Bcl‑2 was mainly increased and reached the highest level at six weeks in the continued hypoxia group. Of note, Bcl‑2 rapidly increased to the peak level at four weeks, followed by a decrease to the lowest level at the eighth week in the intermittent hypoxia group. Bax was generally increased at the late stages under continued hypoxia, but increased at all time-points under the intermittent hypoxia conditions. The two types of hypoxia induced an increase in the MDA content, but a decrease in SOD activity. Marked changes in these two parameters coupled with markedly reduced surviving cells in the hippocampus in a time‑dependent manner were observed in the intermittent hypoxia group in comparison with the continued hypoxia group. OSAS‑induced intermittent hypoxia markedly activated the MAPK signaling pathways, which were triggered by oxidative stress, leading to abnormal expression of downstream Bcl‑2 and Bax, and a severe loss of neural cells in the hippocampus.
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  • CiteScore: 6.9
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Spandidos Publications style
Zhao YN, Wang HY, Li JM, Chen BY, Xia G, Zhang PP and Ge YL: Hippocampal mitogen-activated protein kinase activation is associated with intermittent hypoxia in a rat model of obstructive sleep apnea syndrome. Mol Med Rep 13: 137-145, 2016
APA
Zhao, Y., Wang, H., Li, J., Chen, B., Xia, G., Zhang, P., & Ge, Y. (2016). Hippocampal mitogen-activated protein kinase activation is associated with intermittent hypoxia in a rat model of obstructive sleep apnea syndrome. Molecular Medicine Reports, 13, 137-145. https://doi.org/10.3892/mmr.2015.4505
MLA
Zhao, Y., Wang, H., Li, J., Chen, B., Xia, G., Zhang, P., Ge, Y."Hippocampal mitogen-activated protein kinase activation is associated with intermittent hypoxia in a rat model of obstructive sleep apnea syndrome". Molecular Medicine Reports 13.1 (2016): 137-145.
Chicago
Zhao, Y., Wang, H., Li, J., Chen, B., Xia, G., Zhang, P., Ge, Y."Hippocampal mitogen-activated protein kinase activation is associated with intermittent hypoxia in a rat model of obstructive sleep apnea syndrome". Molecular Medicine Reports 13, no. 1 (2016): 137-145. https://doi.org/10.3892/mmr.2015.4505