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Calcineurin/nuclear factor-κB signaling mediates isoflurane-induced hippocampal neuroinflammation and subsequent cognitive impairment in aged rats.
Mol Med Rep 2017; 15(1):201-209MM

Abstract

It is known that inhaled anesthetics induce neuroinflammation and facilitate postoperative cognitive dysfunction (POCD) in aged individuals; however, the mechanisms by which they mediate these effects remain elusive. Inhalation of the isoflurane anesthetic leads to opening of the mitochondrial permeability transition pore and loss of mitochondrial membrane potential. Therefore, mitochondrial retrograde signaling, which is an adaptive mechanism that facilitates the transmission of signals from dysfunctional mitochondria to the nucleus to activate target gene expression, may be activated during isoflurane inhalation. Therefore, the present study was designed to investigate the role of mitochondrial retrograde signaling in isoflurane-induced hippocampal neuroinflammation and cognitive impairment in aged rats. As calcineurin (CaN) serves an important role in the initiation of mitochondrial retrograde signaling, and nuclear factor-κB (NF‑κB) is involved in CaN signaling, their effects on isoflurane‑induced hippocampal neuroinflammation and cognitive impairment were investigated. Reactive oxygen species and mitochondrial membrane potential fluorescence staining, western blotting, colorimetric analysis, ELISA, immunofluorescence and the Morris water maze test were used in the present study. The results indicate that isoflurane induced hippocampal mitochondrial dysfunction and activated CaN, which subsequently lead to the putative activation of NF‑κB. These resulted in the elevation of interleukin‑1β (IL‑1β) expression (a typical marker of neuroinflammation), and was associated with cognitive impairment in aged rats. In addition, CaN and NF‑κB inhibition attenuated isoflurane-induced neuroinflammation and subsequent cognitive impairment. In conclusion, the results of the present study demonstrate the role of mitochondrial retrograde signaling and associated protein factors in inhaled anesthetic-induced neuroinflammation and cognitive impairment. These protein factors may therefore present promising therapeutic targets for the prevention of POCD.

Authors+Show Affiliations

Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.Department of General Surgery, Peking University Third Hospital, Beijing 100191, P.R. China.Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27909728

Citation

Li, Zhengqian, et al. "Calcineurin/nuclear factor-κB Signaling Mediates Isoflurane-induced Hippocampal Neuroinflammation and Subsequent Cognitive Impairment in Aged Rats." Molecular Medicine Reports, vol. 15, no. 1, 2017, pp. 201-209.
Li Z, Ni C, Xia C, et al. Calcineurin/nuclear factor-κB signaling mediates isoflurane-induced hippocampal neuroinflammation and subsequent cognitive impairment in aged rats. Mol Med Rep. 2017;15(1):201-209.
Li, Z., Ni, C., Xia, C., Jaw, J., Wang, Y., Cao, Y., ... Guo, X. (2017). Calcineurin/nuclear factor-κB signaling mediates isoflurane-induced hippocampal neuroinflammation and subsequent cognitive impairment in aged rats. Molecular Medicine Reports, 15(1), pp. 201-209. doi:10.3892/mmr.2016.5967.
Li Z, et al. Calcineurin/nuclear factor-κB Signaling Mediates Isoflurane-induced Hippocampal Neuroinflammation and Subsequent Cognitive Impairment in Aged Rats. Mol Med Rep. 2017;15(1):201-209. PubMed PMID: 27909728.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Calcineurin/nuclear factor-κB signaling mediates isoflurane-induced hippocampal neuroinflammation and subsequent cognitive impairment in aged rats. AU - Li,Zhengqian, AU - Ni,Cheng, AU - Xia,Chun, AU - Jaw,Joey, AU - Wang,Yujie, AU - Cao,Yiyun, AU - Xu,Mao, AU - Guo,Xiangyang, Y1 - 2016/11/24/ PY - 2015/10/09/received PY - 2016/10/24/accepted PY - 2016/12/3/pubmed PY - 2017/4/4/medline PY - 2016/12/3/entrez SP - 201 EP - 209 JF - Molecular medicine reports JO - Mol Med Rep VL - 15 IS - 1 N2 - It is known that inhaled anesthetics induce neuroinflammation and facilitate postoperative cognitive dysfunction (POCD) in aged individuals; however, the mechanisms by which they mediate these effects remain elusive. Inhalation of the isoflurane anesthetic leads to opening of the mitochondrial permeability transition pore and loss of mitochondrial membrane potential. Therefore, mitochondrial retrograde signaling, which is an adaptive mechanism that facilitates the transmission of signals from dysfunctional mitochondria to the nucleus to activate target gene expression, may be activated during isoflurane inhalation. Therefore, the present study was designed to investigate the role of mitochondrial retrograde signaling in isoflurane-induced hippocampal neuroinflammation and cognitive impairment in aged rats. As calcineurin (CaN) serves an important role in the initiation of mitochondrial retrograde signaling, and nuclear factor-κB (NF‑κB) is involved in CaN signaling, their effects on isoflurane‑induced hippocampal neuroinflammation and cognitive impairment were investigated. Reactive oxygen species and mitochondrial membrane potential fluorescence staining, western blotting, colorimetric analysis, ELISA, immunofluorescence and the Morris water maze test were used in the present study. The results indicate that isoflurane induced hippocampal mitochondrial dysfunction and activated CaN, which subsequently lead to the putative activation of NF‑κB. These resulted in the elevation of interleukin‑1β (IL‑1β) expression (a typical marker of neuroinflammation), and was associated with cognitive impairment in aged rats. In addition, CaN and NF‑κB inhibition attenuated isoflurane-induced neuroinflammation and subsequent cognitive impairment. In conclusion, the results of the present study demonstrate the role of mitochondrial retrograde signaling and associated protein factors in inhaled anesthetic-induced neuroinflammation and cognitive impairment. These protein factors may therefore present promising therapeutic targets for the prevention of POCD. SN - 1791-3004 UR - https://www.unboundmedicine.com/medline/citation/27909728/Calcineurin/nuclear_factor_κB_signaling_mediates_isoflurane_induced_hippocampal_neuroinflammation_and_subsequent_cognitive_impairment_in_aged_rats_ L2 - http://www.spandidos-publications.com/mmr/15/1/201 DB - PRIME DP - Unbound Medicine ER -