Changes in autophagy after traumatic brain injury.
Autophagy is the chief machinery for bulk degradation of superfluous or aberrant cytoplasmic components. This study used the rat moderate fluid percussion injury model to investigate whether the autophagy pathway plays a key role after traumatic brain injury (TBI). Induction of autophagy is manifested by accumulation of autophagosomes (APs), observable under transmission electron microscopy (EM). Two hallmarks of autophagy, i.e., the microtubule-associated protein light chain 3 (LC3)-II and the autophagy-related gene (ATG)12-ATG5 conjugates, were explored by biochemical and confocal microscopic analyses of brain tissues. Under EM, both APs and autolysosomes were markedly accumulated in neurons from 4 h onward after TBI. Western blot analysis showed that ATG12-ATG5 conjugate was markedly redistributed during 5 to 15 days in brain tissues after TBI. LC3-II conjugate was initially unchanged but was drastically upregulated from 24 h onward in the pre-AP-containing fraction after TBI. LC-3 immunostaining was mainly located in living neurons under confocal microscopy. These results clearly show that the autophagy pathway is persistently activated after TBI. Because the autophagy pathway is the chief machinery for bulk elimination of aberrant cell components, we propose that activation of this pathway serves as a protective mechanism for maintaining cellular homeostasis after TBI.
Liu
Cindy L
CL
Neurochemistry Laboratory of Brain Injury, Department of Neurology, University of Miami School of Medicine, Miami, Florida 33136, USA. cliu@med.Miami.edu
Chen
Shaoyi
S
Dietrich
Dalton
D
Hu
Bingren R
BR
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D001930:Brain Injuries / Q000473:pathology* / Q000503:physiopathology*; D015870:Gene Expression; D007150:Immunohistochemistry; D008247:Lysosomes / Q000378:metabolism / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D009474:Neurons / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D025841:Small Ubiquitin-Related Modifier Proteins / Q000096:biosynthesis
D008869:Microtubule-Associated Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; C526109:Anxa3 protein, rat