Effect of premortem and postmortem factors on the distribution and preservation of antioxidant activities in the cytosol and synaptosomes of human brains.

Abstract

The human brain displays oxidant and antioxidant markers with regional specificity that directly impinges on neuronal function in aging and in disease states. Similarly, the antioxidant activities might exhibit differential intracellular distribution rendering subcellular structures differentially vulnerable to toxic insults. To investigate the subcellular distribution of antioxidant activities in the human postmortem brain, we assayed superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST) in the cytosol and synaptosomal fraction from the frontal cortex (FC) of 45 postmortem human brains. We also tested whether these activities were altered by premortem and postmortem factors, including increasing storage time (11.8-104.1 months), postmortem interval (PMI) (2.5-26 h), age and gender differences, and agonal state [based on Glasgow coma scale (GCS): range: 3-15]. Overall, the antioxidant activities were found to be several folds lower in the synaptosomes compared to cytosol, which could make it more susceptible to degeneration. The activities were significantly affected mainly by age (SOD increased in synaptosomes, p=0.01; GSH decreased in cytosol, p=0.03; GPx decreased in cytosol and increased in synaptosomes, p=0.05; GST decreased in synaptosomes, p=0.05) and to a lesser extent by other premortem (GST decreased with GCS in synaptosomes, p=0.02) and postmortem factors (GSH decreased with PMI in cytosol, p=0.04). Increasing storage time or gender difference did not affect the antioxidant activities. We infer that premortem and postmortem factors in general, and increasing age in particular, significantly alter the antioxidant activities in subcellular fractions of postmortem brain with implications for studies on brain pathology employing stored human samples.