Mitochondrial cytochrome c oxidase expression in the central nervous system is elevated at sites of pressure gradient elevation but not absolute pressure increase.
The paucity of suitable experimental models has made it difficult to isolate the pathogenic role of mitochondria in central nervous system diseases associated with absolute pressure elevation and increased pressure gradients. Experimental models of traumatic brain injury (TBI) and hydrocephalus have been useful for examining the mitochondrial response following pressure increase in the central nervous system; however, the presence of multiple pathogenic factors acting on the brain in these previous studies has made it difficult to determine whether the induced changes were a result of mechanical damage, intracranial pressure elevation, or other pathogenic factors. By direct monitoring and control of pressures in the intraocular, intracranial, and vascular compartments, we use the pig optic nerve, a typical central white matter tract, to compare the temporal sequence of cytochrome c oxidase (CcO) levels between regions of absolute pressure elevation and pressure gradient increase. We demonstrate that a rise in pressure gradient without traumatic injury up-regulates CcO levels across the site of the gradient, in a manner similar to what has been previously reported for hydrocephalus. We also demonstrate that CcO changes do not occur following an absolute pressure rise. These findings taken together with our recent reports suggest that mitochondria initiate an early compensatory response to axonal damage following pressure gradient increase. Extrapolation of our results also suggests that decreased CcO levels in TBI may be secondary to mechanical damage. This study emphasises the importance of pressure gradients in regulating mitochondrial function in the central nervous system.
Balaratnasingam
Chandrakumar
C
Centre for Ophthalmology and Visual Science and the ARC Centre of Excellence in Vision Science, The University of Western Australia, Perth, Western Australia, Australia.
Pham
Duy
D
Morgan
William H
WH
Bass
Louise
L
Cringle
Stephen J
SJ
Yu
Dao-Yi
DY
D000818:Animals; D001370:Axonal Transport; D001794:Blood Pressure; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D003576:Electron Transport Complex IV / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D007427:Intracranial Pressure; D007429:Intraocular Pressure; D008928:Mitochondria / Q000201:enzymology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009798:Ocular Hypertension / Q000201:enzymology* / Q000473:pathology; D009900:Optic Nerve / Q000201:enzymology* / Q000648:ultrastructure; D015203:Reproducibility of Results; D034421:Sus scrofa
D009419:Nerve Tissue Proteins; D003576:Electron Transport Complex IV