한빛사논문
- 조회1,867
Sangjune Kim,1,2,11 Seung-Hwan Kwon,1,2,11 Tae-In Kam,1,2 Nikhil Panicker,1,2 Senthilkumar S. Karuppagounder,1,2 Saebom Lee,1,2 Jun Hee Lee,1,2,9 Wonjoong Richard Kim,1,2 Minjee Kook,1,2 Catherine A. Foss,3 Chentian Shen,3,10 Hojae Lee,1,2 Subhash Kulkarni,4 Pankaj J. Pasricha,4 Gabsang Lee,1,2,5 Martin G. Pomper,3 Valina L. Dawson,1,2,5,6 Ted M. Dawson,1,2,5,7,12,* and Han Seok Ko1,2,8,*
1 Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
2 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
3 The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
4 Center for Neurogastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
5 Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
6 Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
7 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
8 Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130, USA
9 Present address: Department of Pharmacology and Toxicology, University of Alabama at Birmingham School of Medicine, Birmingham,AL 35294, USA
10 Present address: Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
11 These authors contributed equally
12 Lead Contact
*Correspondence: Ted M. Dawson, Han Seok Ko
Abstract
Analysis of human pathology led Braak to postulate that α-synuclein (α-syn) pathology could spread from the gut to brain via the vagus nerve. Here, we test this postulate by assessing α-synucleinopathy in the brain in a novel gut-to-brain α-syn transmission mouse model, where pathological α-syn preformed fibrils were injected into the duodenal and pyloric muscularis layer. Spread of pathologic α-syn in brain, as assessed by phosphorylation of serine 129 of α-syn, was observed first in the dorsal motor nucleus, then in caudal portions of the hindbrain, including the locus coeruleus, and much later in basolateral amygdala, dorsal raphe nucleus, and the substantia nigra pars compacta. Moreover, loss of dopaminergic neurons and motor and non-motor symptoms were observed in a similar temporal manner. Truncal vagotomy and α-syn deficiency prevented the gut-to-brain spread of α-synucleinopathy and associated neurodegeneration and behavioral deficits. This study supports the Braak hypothesis in the etiology of idiopathic Parkinson’s disease (PD).
논문정보
- Research article
- 2019년 06월 (BRIC 등록일 2019-07-02)
- 국외 연구진
- 생명과학 > 신경생물학
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