Hierarchical Studies in TRAP2 Mice Demonstrate that Neuronal Activation and Mitochondrial Networks Integration Constitute the Key Mechanism Underlying Painful Syncope
Xueyin Pu1 · Yulu Xia1 · Ziwei Ni4 · Changlei Zhu1 · Kunlong Zhang3 · Bozhi Liu1 · Rui Lin1 · Jingxuan Zhu1 · Hui Liu1 · Shujiao Li1 · Yunqiang Huang1 · Feifei Wu1 · Nannan Liu1 · Shuai Zhang1 · Yousheng Wu1 · Fei Tian1 · Yanling Yang2 · Yayun Wang1
1 School of Basic Medical Sciences, Fourth Military Medical University, Laboratory of Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, Xi’an 710032, China
2 Department of Hepatobiliary Surgery, First Affiliated Hospital of Fourth Military Medical University, Xi’an 710032, China
3 Department of Rehabilitation and Physical Therapy, First Affiliated Hospital of Fourth Military Medical University, Xi’an 710032, China
4 School of Medicine, Yan’an University, Yan’an 716000, China
Abstract
Approximately 40% of the global population experiences at least one syncope episode during their lifetime. However, the neurobiological mechanisms underlying these effects remain unclear. In this study, facial administration of formalin in mice was used to induce painful syncope. Whole-brain atlas analysis of 116,283 c-Fos+ neurons in 856 brain regions revealed 11 key brain regions associated with painful syncope. Subsequent analysis of approximately 300,000 mitochondrial networks revealed that their morphology in the locus coeruleus (LC), nucleus tractus solitarius (NTS), gigantocellular reticular nucleus (GR), lateral reticular nucleus (LRN), and parabrachial nucleus, spinal trigeminal nucleus pars caudalis (SPVC) underwent significant changes during syncope. Furthermore, downregulation of the mitochondrial dynamin-related protein 1 (DRP1) in the NTS could mediate the exacerbation of weakly lying on the ground in painful syncope. Our findings reveal that abnormal neuronal activity and mitochondrial network remodeling may serve as key mechanisms underlying painful syncope.
Keywords
Painful syncope; Neuronal activation; Mitochondrial networks; Coordination; TRAP2-tdTomato mice; TRAP2-MITO-GFP mice
