Dorsal raphe nucleus to pre-Bötzinger complex serotonergic neural circuit is involved in seizure-induced respiratory arrest

HaiXiang Ma; Qian Yu; Yue Shen; XiTing Lian; LeYuan Gu; YuLing Wang; Qing Xu; Han Lu; HaiTing Zhao; Chang Zeng; Kazuki Nagayasu; HongHai Zhang

iScience (Oct 2022)

Dorsal raphe nucleus to pre-Bötzinger complex serotonergic neural circuit is involved in seizure-induced respiratory arrest

HaiXiang Ma,
Qian Yu,
Yue Shen,
XiTing Lian,
LeYuan Gu,
YuLing Wang,
Qing Xu,
Han Lu,
HaiTing Zhao,
Chang Zeng,
Kazuki Nagayasu,
HongHai Zhang

Affiliations

HaiXiang Ma: Department of Anesthesiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China
Qian Yu: Department of Anesthesiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China
Yue Shen: Department of Anesthesiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China; Department of Anesthesiology, Hangzhou First People’s Hospital, Nanjing Medical University, Hangzhou 310006, China
XiTing Lian: Department of Anesthesiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
LeYuan Gu: Department of Anesthesiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China
YuLing Wang: Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China
Qing Xu: Department of Anesthesiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
Han Lu: Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
HaiTing Zhao: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
Chang Zeng: Health Management Center, Xiangya Hospital, Central South University, Changsha 410008
Kazuki Nagayasu: Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan
HongHai Zhang: Department of Anesthesiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China; Department of Anesthesiology, Hangzhou First People’s Hospital, Nanjing Medical University, Hangzhou 310006, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310006, China; Corresponding author

Journal volume & issue: Vol. 25, no. 10
p. 105228

Abstract

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Summary: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death among patients with epilepsy. However, the underlying mechanism of SUDEP remains elusive. Previous studies showed seizure-induced respiratory arrest (S-IRA) is the main factor in SUDEP, and that enhancement of serotonin (5-HT) function in the dorsal raphe nucleus (DR) can significantly reduce the incidence of S-IRA in the DBA/1 mouse model of SUDEP. The pre-Bötzinger complex (PBC), known for its role in regulating respiratory rhythm, can express the 5-HT2A receptor (5-HT2AR). Here, using the pharmacological and optogenetic methods, respectively, we observed that the serotonergic neural circuit between DR and PBC was involved in S-IRA evoked by either acoustic stimulation or pentylenetetrazole (PTZ) injection in the DBA/1 mice, and found 5-HT2AR located in PBC plays an important role in it. Our findings will further significantly improve our understanding of SUDEP and provide a promising therapeutic target for SUDEP prevention.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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