Investigation of the roles of CCAAT/enhancer binding protein delta (CEBPD) in astrogliosis after spinal cord injury

  • 邱 乃恩

Student thesis: Master's Thesis

Abstract

Spinal cord injury (SCI) is a common and devastating central nervous system (CNS) disease that results in disruption of cord microstructure and is followed by limited neuronal regeneration and functional recovery impairment After SCI astrocytes the most abundant glial cells in the CNS become reactive and hypertrophy Astrogliosis is an increase in the number of astrocytes to above-normal levels that can be observed in all CNS injuries and neuroinflammatory diseases In severe cases of injury astrogliosis results in the formation of irreversible glia scarring that acts as a regeneration barrier Thus investigation targeting on astrocyte activation and glial scar formation could be useful for SCI therapy Transcription factor CCAAT/enhancer binding protein delta (CEBPD) is responsive to inflammatory factors such as tumor necrosis factor alpha (TNF-?) and interleukin 1 beta (IL-1β) and has been observed in many inflammation-related diseases including AD In SCI mice our results showed that CEBPD is expressed in reactive astrocyte border Using animal behavior tests we found that a better recovered effect was observed in injured Cebpd-deficient mice Our results showed that increase of CEBPD in astrocytes inhibited their self-migration ability through the RhoA pathway upon IL-1β treatment In addition the conditioned medium of astrocyte expressing CEBPD could promote the migration of inactive astrocytes We further identified matrix metalloproteinase-3 (MMP-3) was responsive to CEBPD in astrocytes through a transcriptional regulation Taken together the results suggested that the migration inactive astrocytes can be promoted by MMP3 secreted from the fixed activated astrocyte expressing CEBPD which contributes to the formation of glial scar in SCI
Date of Award2014 Jul 30
Original languageEnglish
SupervisorJu-Ming Wang (Supervisor)

Cite this

Investigation of the roles of CCAAT/enhancer binding protein delta (CEBPD) in astrogliosis after spinal cord injury
乃恩, 邱. (Author). 2014 Jul 30

Student thesis: Master's Thesis