Intrinsic differences in brain and spinal cord mitochondria: Implication for therapeutic interventions.
It is well known that regions of the CNS differentially respond to insults. After brain injury, cyclosporine A reduces damage but is ineffective following spinal cord injury. We address this disparity by assessing several parameters of mitochondrial physiology in the normal neocortex and spinal cord. In situ measurements of O(2) (-.) production, lipid peroxidation, and mitochondrial DNA oxidation revealed significantly higher levels in spinal cord vs. neocortical neurons. Real-time PCR demonstrated differences in mitochondrial transcripts coupled with decreases in complex I enzyme activity and respiration in spinal cord mitochondria. The threshold for calcium-induced mitochondrial permeability transition was substantially reduced in spinal cord vs. neocortex and modulated by lipid peroxidation. These intrinsic differences may provide a pivotal target for strategies to ameliorate neuronal damage following injury, and this imbalance in oxidative stress may contribute to the susceptibility of spinal cord motor neurons in neuropathologies such as amyotrophic lateral sclerosis.
Sullivan
Patrick G
PG
Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, Kentucky 40536, USA. patsull@uky.edu
Rabchevsky
Alexander G
AG
Keller
Jeffery N
JN
Lovell
Mark
M
Sodhi
Ajeet
A
Hart
Ronald P
RP
Scheff
Stephen W
SW
D000447:Aldehydes; D000818:Animals; D015153:Blotting, Western; D004272:DNA, Mitochondrial / Q000378:metabolism; D042967:Electron Transport Complex I / Q000032:analysis / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008928:Mitochondria / Q000502:physiology*; D010084:Oxidation-Reduction; D016548:Prosencephalon / Q000502:physiology / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000502:physiology / Q000648:ultrastructure*
D000447:Aldehydes; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D042967:Electron Transport Complex I; C027576:4-hydroxy-2-nonenal