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Chemogenetic attenuation of cortical seizures in nonhuman primates

Author

Listed:
  • Naohisa Miyakawa

    (National Institutes for Quantum Science and Technology)

  • Yuji Nagai

    (National Institutes for Quantum Science and Technology)

  • Yukiko Hori

    (National Institutes for Quantum Science and Technology)

  • Koki Mimura

    (National Institutes for Quantum Science and Technology)

  • Asumi Orihara

    (National Institutes for Quantum Science and Technology
    Tokyo Medical and Dental University)

  • Kei Oyama

    (National Institutes for Quantum Science and Technology)

  • Takeshi Matsuo

    (Tokyo Metropolitan Neurological Hospital)

  • Ken-ichi Inoue

    (Kyoto University)

  • Takafumi Suzuki

    (National Institute of Information and Communications Technology)

  • Toshiyuki Hirabayashi

    (National Institutes for Quantum Science and Technology)

  • Tetsuya Suhara

    (National Institutes for Quantum Science and Technology)

  • Masahiko Takada

    (Kyoto University)

  • Makoto Higuchi

    (National Institutes for Quantum Science and Technology)

  • Keisuke Kawasaki

    (Niigata University School of Medicine)

  • Takafumi Minamimoto

    (National Institutes for Quantum Science and Technology)

Abstract

Epilepsy is a disorder in which abnormal neuronal hyperexcitation causes several types of seizures. Because pharmacological and surgical treatments occasionally interfere with normal brain function, a more focused and on-demand approach is desirable. Here we examined the efficacy of a chemogenetic tool—designer receptors exclusively activated by designer drugs (DREADDs)—for treating focal seizure in a nonhuman primate model. Acute infusion of the GABAA receptor antagonist bicuculline into the forelimb region of unilateral primary motor cortex caused paroxysmal discharges with twitching and stiffening of the contralateral arm, followed by recurrent cortical discharges with hemi- and whole-body clonic seizures in two male macaque monkeys. Expression of an inhibitory DREADD (hM4Di) throughout the seizure focus, and subsequent on-demand administration of a DREADD-selective agonist, rapidly suppressed the wide-spread seizures. These results demonstrate the efficacy of DREADDs for attenuating cortical seizure in a nonhuman primate model.

Suggested Citation

  • Naohisa Miyakawa & Yuji Nagai & Yukiko Hori & Koki Mimura & Asumi Orihara & Kei Oyama & Takeshi Matsuo & Ken-ichi Inoue & Takafumi Suzuki & Toshiyuki Hirabayashi & Tetsuya Suhara & Masahiko Takada & M, 2023. "Chemogenetic attenuation of cortical seizures in nonhuman primates," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36642-6
    DOI: 10.1038/s41467-023-36642-6
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    References listed on IDEAS

    as
    1. Yuji Nagai & Erika Kikuchi & Walter Lerchner & Ken-ichi Inoue & Bin Ji & Mark A. G. Eldridge & Hiroyuki Kaneko & Yasuyuki Kimura & Arata Oh-Nishi & Yukiko Hori & Yoko Kato & Toshiyuki Hirabayashi & At, 2016. "PET imaging-guided chemogenetic silencing reveals a critical role of primate rostromedial caudate in reward evaluation," Nature Communications, Nature, vol. 7(1), pages 1-8, December.
    2. Dennis Kätzel & Elizabeth Nicholson & Stephanie Schorge & Matthew C. Walker & Dimitri M. Kullmann, 2014. "Chemical–genetic attenuation of focal neocortical seizures," Nature Communications, Nature, vol. 5(1), pages 1-9, September.
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    Cited by:

    1. Toshiyuki Hirabayashi & Yuji Nagai & Yuki Hori & Yukiko Hori & Kei Oyama & Koki Mimura & Naohisa Miyakawa & Haruhiko Iwaoki & Ken-ichi Inoue & Tetsuya Suhara & Masahiko Takada & Makoto Higuchi & Takaf, 2024. "Multiscale chemogenetic dissection of fronto-temporal top-down regulation for object memory in primates," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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