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Phospholipase C-related inactive protein type-1 deficiency affects anesthetic electroencephalogram activity induced by propofol and etomidate in mice

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Abstract

Purpose

The general anesthetics propofol and etomidate mainly exert their anesthetic actions via GABA A receptor (GABAA-R). The GABAA-R activity is influenced by phospholipase C-related inactive protein type-1 (PRIP-1), which is related to trafficking and subcellular localization of GABAA-R. PRIP-1 deficiency attenuates the behavioral reactions to propofol but not etomidate. However, the effect of these anesthetics and of PRIP-1 deficiency on brain activity of CNS are still unclear. In this study, we examined the effects of propofol and etomidate on the electroencephalogram (EEG).

Methods

The cortical EEG activity was recorded in wild-type (WT) and PRIP-1 knockout (PRIP-1 KO) mice. All recorded EEG data were offline analyzed, and the power spectral density and 95% spectral edge frequency of EEG signals were compared between genotypes before and after injections of anesthetics.

Results

PRIP-1 deficiency induced increases in EEG absolute powers, but did not markedly change the relative spectral powers during waking and sleep states in the absence of anesthesia. Propofol administration induced increases in low-frequency relative EEG activity and decreases in SEF95 values in WT but not in PRIP-1 KO mice. Following etomidate injection, low-frequency EEG power was increased in both genotype groups. At high frequency, the relative power in PRIP-1 KO mice was smaller than that in WT mice.

Conclusions

The lack of PRIP-1 disrupted the EEG power distribution, but did not affect the depth of anesthesia after etomidate administration. Our analyses suggest that PRIP-1 is differentially involved in anesthetic EEG activity with the regulation of GABAA-R activity.

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Acknowledgements

This work was supported by Grant-in-Aid for Young Scientists (B) #JP16K20888 (to T. F.), Grants-in-Aid for Scientific Research (C) # JP18K08846 (to S. U.), and a Hirosaki University Institutional Research Grant (to S. U.). All authors concur that there is no conflict of interest with regard to manuscript.

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Author notes

  1. Tomonori Furukawa and Yoshikazu Nikaido contributed equally to this work.

Authors and Affiliations

  1. Department of Neurophysiology, Hirosaki University Graduate School of Medicine, 5 Zaihu-cho, Hirosaki, Aomori, 036-8562, Japan

    Tomonori Furukawa, Yoshikazu Nikaido, Shuji Shimoyama, Yoshiki Ogata & Shinya Ueno

  2. Department of Anesthesiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

    Yoshikazu Nikaido, Tetsuya Kushikata & Kazuyoshi Hirota

  3. Research Center for Child Mental Development, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

    Shinya Ueno

  4. Department of Cellular and Molecular Pharmacology, Division of Basic Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Takashi Kanematsu

  5. School of Dental Medicine, Fukuoka Dental College, Fukuoka, Japan

    Masato Hirata

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  1. Tomonori Furukawa
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Furukawa, T., Nikaido, Y., Shimoyama, S. et al. Phospholipase C-related inactive protein type-1 deficiency affects anesthetic electroencephalogram activity induced by propofol and etomidate in mice. J Anesth 33, 531–542 (2019). https://doi.org/10.1007/s00540-019-02663-z

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