Mitochondrial function in human brains is affected by pre- and post mortem factors.
OBJECTIVE
Mitochondrial function and the ensuing ATP synthesis are central to the functioning of the brain and contribute to neuronal physiology. Most studies on neurodegenerative diseases have highlighted that mitochondrial dysfunction is an important event contributing to pathology. However, studies on the human brain mitochondria in various neurodegenerative disorders heavily rely on post mortem samples. As post mortem tissues are influenced by pre- and post mortem factors, we investigated the effect of these variables on mitochondrial function.


METHODS
We examined whether the mitochondrial function (represented by mitochondrial enzymes and antioxidant activities) in post mortem human brains (n=45) was affected by increased storage time (11.8-104.1 months), age of the donor (2 days to 80 years), post mortem interval (2.5-26 h), gender difference and agonal state [based on Glasgow Coma Scale: range=3-15] in the frontal cortex, as a prototype.


RESULTS
We observed that the activities of citrate synthase, succinate dehydrogenase and mitochondrial reductase (MTT) were significantly affected only by gender difference (citrate synthase: P=0.005; succinate dehydrogenase: P=0.01; mitochondrial reductase: P=0.006), being higher in females, but not by any other factor. Mitochondrial complex I activity was significantly inhibited by increasing age (r=-0.40; P=0.05). On the other hand, the mitochondrial antioxidant enzyme glutathione reductase decreased with severe agonal state (P=0.003), while the activity of glutathione-S-transferase declined with increased storage time (P=0.005) and severe agonal state (P=0.02).


CONCLUSIONS
Our data highlight the influence of pre- and post mortem factors on preservation of mitochondrial function with implications for studies on brain pathology employing stored human samples.
Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India.
G
G
Harish
C
C
Venkateshappa
A
A
Mahadevan
N
N
Pruthi
M M S
MM
Bharath
S K
SK
Shankar
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D045222:Electron Transport Chain Complex Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D010338:Pathology, Clinical; D011180:Postmortem Changes; D055815:Young Adult
D045222:Electron Transport Chain Complex Proteins