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Article

Conflicting Actions of Inhalational Anesthetics, Neurotoxicity and Neuroprotection, Mediated by the Unfolded Protein Response

by 1,†, 1,†, 2 and 3,*
1
Department of Anesthesiology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
2
Department of Anesthesiology, Chiba Rosai Hospital, Ichihara 299-0003, Japan
3
Department of Medicine, Pain Center, Chiba Medical Center, Teikyo University, Ichihara 299-0111, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(2), 450; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020450
Received: 9 December 2019 / Revised: 2 January 2020 / Accepted: 8 January 2020 / Published: 10 January 2020
(This article belongs to the Special Issue Molecular Mechanisms and Neural Correlates of General Anesthesia)
Preclinical studies have shown that exposure of the developing brain to inhalational anesthetics can cause neurotoxicity. However, other studies have claimed that anesthetics can exert neuroprotective effects. We investigated the mechanisms associated with the neurotoxic and neuroprotective effects exerted by inhalational anesthetics. Neuroblastoma cells were exposed to sevoflurane and then cultured in 1% oxygen. We evaluated the expression of proteins related to the unfolded protein response (UPR). Next, we exposed adult mice in which binding immunoglobulin protein (BiP) had been mutated, and wild-type mice, to sevoflurane, and evaluated their cognitive function. We compared our results to those from our previous study in which mice were exposed to sevoflurane at the fetal stage. Pre-exposure to sevoflurane reduced the expression of CHOP in neuroblastoma cells exposed to hypoxia. Anesthetic pre-exposure also significantly improved the cognitive function of adult wild-type mice, but not the mutant mice. In contrast, mice exposed to anesthetics during the fetal stage showed cognitive impairment. Our data indicate that exposure to inhalational anesthetics causes endoplasmic reticulum (ER) stress, and subsequently leads to an adaptive response, the UPR. This response may enhance the capacity of cells to adapt to injuries and improve neuronal function in adult mice, but not in developing mice. View Full-Text
Keywords: anesthetics; chaperone; endoplasmic reticulum; ER stress; KDEL receptor; unfolded protein response; neuroprotection; neurotoxicity anesthetics; chaperone; endoplasmic reticulum; ER stress; KDEL receptor; unfolded protein response; neuroprotection; neurotoxicity
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MDPI and ACS Style

Kokubun, H.; Jin, H.; Komita, M.; Aoe, T. Conflicting Actions of Inhalational Anesthetics, Neurotoxicity and Neuroprotection, Mediated by the Unfolded Protein Response. Int. J. Mol. Sci. 2020, 21, 450. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020450

AMA Style

Kokubun H, Jin H, Komita M, Aoe T. Conflicting Actions of Inhalational Anesthetics, Neurotoxicity and Neuroprotection, Mediated by the Unfolded Protein Response. International Journal of Molecular Sciences. 2020; 21(2):450. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020450

Chicago/Turabian Style

Kokubun, Hiroshi, Hisayo Jin, Mari Komita, and Tomohiko Aoe. 2020. "Conflicting Actions of Inhalational Anesthetics, Neurotoxicity and Neuroprotection, Mediated by the Unfolded Protein Response" International Journal of Molecular Sciences 21, no. 2: 450. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020450

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