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

• Published in: iScience 2023-04, Vol.26 (4), p.106284-106284, Article 106284
• Main Authors: Lian, XiTing, Xu, Qing, Wang, YuLing, Gu, LeYuan, Yu, Qian, Shao, WeiHui, Ma, HaiXiang, Shen, Yue, Liu, Lu, Gu, JiaXuan, Zhang, HongHai
• Format: Article
• Language: English
• Subjects: Molecular physiology; Neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106284

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. [Display omitted] •Esmolol can significantly reverse the effect of atomoxetine on reducing S-IRA•Cardiac arrhythmias that occur with S-IRA can be alleviated by atomoxetine•The noradrenergic neural circuit between LC and heart is involved in modulating SUDEP•β1-AR on cardiomyocytes may be a specific target for preventing SUDEP Molecular physiology; Neuroscience