Open Access

Epigenetic modulation of the MAPK pathway prevents isoflurane‑induced neuronal apoptosis and cognitive decline in aged rats

  • Authors:
    • Lei Huang
    • Hai‑Bin Fang
    • Hui‑Hui Cheng
    • Sheng‑Lan Mei
    • Yun‑Ping Cheng
    • Yao Lv
    • Qing-Tao Meng
    • Zhong‑Yuan Xia
  • View Affiliations

  • Published online on: September 1, 2020     https://doi.org/10.3892/etm.2020.9162
  • Article Number: 35
  • Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Isoflurane is a broadly used inhalation anesthetic that causes cognitive impairment in rodent models as well as humans. Although previous studies suggested an association between isoflurane exposure and neuro‑inflammation, apoptosis and mitochondrial dysfunction, the pathogenesis of isoflurane‑induced cognitive decline remains elusive. In the present study, 22‑month‑old male Sprague‑Dawley male rats (n=96) were divided into three groups: Control (Cont), isoflurane (ISO) and MS‑275 pre‑treated groups. The rats were sacrificed following exposure to isoflurane and a cognitive test. The hippocampus of each animal was harvested for quantitative PCR, TUNEL staining and western blot analysis. Histone deacetylases (HDAC)‑1, ‑2 and ‑3 exhibited a significant increase at the gene and protein expression levels, whereas negligible mRNA expressions were observed for genes HDAC 4‑11 (P>0.05; compared with Cont). Pre‑treatment with the HDAC inhibitor MS‑275 significantly inhibited the increase in TUNEL‑positive cells induced by isoflurane exposure (70.72% decrease; P<0.001; compared with ISO). Furthermore, MS‑275 significantly decreased caspase‑3 and Bax expression levels while increasing Bcl‑2 protein expression. The isoflurane‑induced changes in the MAPK pathway signaling proteins ERK1/2, JNK and p38 were also reversed with MS‑275 pre‑treatment. Finally, in a Morris water maze test, the time to find a hidden platform was reduced in MS‑275 pre‑treated rats, compared with the ISO group. Therefore, the present study provided insight into the effect of isoflurane exposure on neuronal apoptosis pathways, as well as cognitive decline via epigenetic programming of MAPK signaling in aged rats.
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November-2020
Volume 20 Issue 5

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Online ISSN:1792-1015

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Spandidos Publications style
Huang L, Fang HB, Cheng HH, Mei SL, Cheng YP, Lv Y, Meng Q and Xia ZY: Epigenetic modulation of the MAPK pathway prevents isoflurane‑induced neuronal apoptosis and cognitive decline in aged rats. Exp Ther Med 20: 35, 2020.
APA
Huang, L., Fang, H., Cheng, H., Mei, S., Cheng, Y., Lv, Y. ... Xia, Z. (2020). Epigenetic modulation of the MAPK pathway prevents isoflurane‑induced neuronal apoptosis and cognitive decline in aged rats. Experimental and Therapeutic Medicine, 20, 35. https://doi.org/10.3892/etm.2020.9162
MLA
Huang, L., Fang, H., Cheng, H., Mei, S., Cheng, Y., Lv, Y., Meng, Q., Xia, Z."Epigenetic modulation of the MAPK pathway prevents isoflurane‑induced neuronal apoptosis and cognitive decline in aged rats". Experimental and Therapeutic Medicine 20.5 (2020): 35.
Chicago
Huang, L., Fang, H., Cheng, H., Mei, S., Cheng, Y., Lv, Y., Meng, Q., Xia, Z."Epigenetic modulation of the MAPK pathway prevents isoflurane‑induced neuronal apoptosis and cognitive decline in aged rats". Experimental and Therapeutic Medicine 20, no. 5 (2020): 35. https://doi.org/10.3892/etm.2020.9162