Noradrenergic pathway from the locus coeruleus to heart is implicated in modulating SUDEP

XiTing Lian; Qing Xu; YuLing Wang; LeYuan Gu; Qian Yu; WeiHui Shao; HaiXiang Ma; Yue Shen; Lu Liu; JiaXuan Gu; HongHai Zhang

doi:10.1016/j.isci.2023.106284

Noradrenergic pathway from the locus coeruleus to heart is implicated in modulating SUDEP

iScience. 2023 Feb 27;26(4):106284. doi: 10.1016/j.isci.2023.106284. eCollection 2023 Apr 21.

Authors

XiTing Lian¹, Qing Xu¹, YuLing Wang², LeYuan Gu², Qian Yu², WeiHui Shao², HaiXiang Ma², Yue Shen¹, Lu Liu¹, JiaXuan Gu¹, HongHai Zhang^{1

2

3}

Affiliations

¹ Department of Anesthesiology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
² Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China.
³ Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310006, China.

Abstract

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death among epilepsy patients. However, the underlying mechanism remains elusive. Seizure-induced respiratory arrest (S-IRA) is recognized as a main cause of SUDEP, but the contribution of other factors such as cardiac arrhythmias cannot be excluded. Here, we found that both the locus coeruleus (LC) and peripheral noradrenergic neurotransmission were involved in S-IRA and the protective effect of atomoxetine in reducing the occurrence of S-IRA and SUDEP could be reversed by esmolol hydrochloride. Moreover, we investigated the connection between the LC and heart implicated in the modulation of SUDEP by fiber photometry. These data suggested that noradrenergic neurons in the LC might regulate the occurrence of SUDEP through β1-adrenergic receptors on cardiomyocytes. Overall, our findings indicate the involvement of the brain-heart axis in modulating S-IRA and SUDEP and, therefore, will open a new perspective on decoding SUDEP.

Keywords: Molecular physiology; Neuroscience.