Chemogenetic attenuation of cortical seizures in nonhuman primates

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, Makoto Higuchi, Keisuke Kawasaki and Takafumi Minamimoto ()
Additional contact information
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
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

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36642-6

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