Spreading of TDP-43 pathology via pyramidal tract induces ALS-like phenotypes in TDP-43 transgenic mice

Autor: Xuebing Ding, Zhi Xiang, Chi Qin, Yongkang Chen, Haiyan Tian, Lin Meng, Danhao Xia, Han Liu, Jia Song, Jun Fu, Mingming Ma, Xuejing Wang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Acta Neuropathologica Communications, Vol 9, Iss 1, Pp 1-17 (2021)
Druh dokumentu: article
ISSN: 2051-5960
DOI: 10.1186/s40478-020-01112-3
Popis: Abstract Transactive response DNA-binding protein 43 kDa (TDP-43) has been identified as the major component of ubiquitinated inclusions found in patients with sporadic amyotrophic lateral sclerosis (ALS). Increasing evidence suggests prion-like transmission of TDP-43 aggregates via neuroanatomic connection in vitro and pyramidal tract in vivo. However, it is still unknown whether the spreading of pathological TDP-43 sequentially via pyramidal tract can initiate ALS-like pathology and phenotypes. In this study, we reported that injection of TDP-43 preformed fibrils (PFFs) into the primary motor cortex (M1) of Thy1-e (IRES-TARDBP) 1 mice induced the spreading of pathological TDP-43 along pyramidal tract axons anterogradely. Moreover, TDP-43 PFFs-injected Thy1-e (IRES-TARDBP) 1 mice displayed ALS-like neuropathological features and symptoms, including motor dysfunctions and electrophysiological abnormalities. These findings provide direct evidence that transmission of pathological TDP-43 along pyramidal tract induces ALS-like phenotypes, which further suggest the potential mechanism for TDP-43 proteinopathy.
Databáze: Directory of Open Access Journals
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