TDP-43 proteolysis is associated with astrocyte reactivity after traumatic brain injury in rodents

Chih Yuan Huang, Yi Che Lee, Ping Chia Li, Po Chou Liliang, Kang Lu, Kuo Wei Wang, Li Ching Chang, Li Yen Shiu, Ming Feng Chen, Yuan Ting Sun, Hao kuang Wang

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

The aggregation and deposition of transactivation response DNA-binding protein 43 (TDP-43) in neurons and astrocytes is characteristic in a number of neurodegenerative diseases including Alzheimer's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis. Nevertheless, the exact role of TDP-43 in astrocytes is unknown. Recently, TDP-43 was identified in neurons but not astrocytes after traumatic brain injury (TBI) in humans. In the present study, we evaluated TDP-43 expression and proteolysis in astrocytes in a rat model of TBI. We assessed TDP-43 fragment expression, astrocyte morphology, neuronal population numbers, and motor function after TBI with or without intracerebroventricular administration of a caspase-3 inhibitor. Motor dysfunction was observed after TBI in potential association astrocytic TDP-43 short fragment mislocalization and accumulation, astrogliosis, and neuronal loss. Notably, caspase-3 inhibition prevented these changes after TBI. Our findings suggest that TDP-43 proteolysis in astrocytes is related to astrogliosis and subsequent neuronal loss in TBI, and that TDP-43 may be an important therapeutic target for preventing motor dysfunction after TBI.

Original languageEnglish
Pages (from-to)61-68
Number of pages8
JournalJournal of Neuroimmunology
Volume313
DOIs
Publication statusPublished - 2017 Dec 15

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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