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Published on: June 28, 2024
Glutathione metabolism is modulated by postmortem interval, gender difference and agonal state in postmortem human
G Harish1, C Venkateshappa, Anita Mahadevan
1Department of Neurochemistry, National Institute of Mental Health and Neurosciences-NIMHANS, Bangalore, India.
Postmortem factors significantly alter glutathione levels and related enzymes in human brain tissue, but not SOD or catalase. These changes vary by brain region, gender, and agonal state, impacting brain pathology research.
Area of Science:
- Neuroscience
- Biochemistry
- Forensic Science
Background:
- Oxidative stress and antioxidant balance are crucial in brain pathology.
- Postmortem human brain studies are limited by pre- and postmortem factors affecting biological markers.
- Understanding these factors is vital for accurate interpretation of brain tissue analyses.
Purpose of the Study:
- To investigate the impact of postmortem interval (PMI), gender, and agonal state on antioxidant enzymes and glutathione markers in various human brain regions.
- To identify brain regions with greater stability for specific biochemical markers.
Main Methods:
- Analysis of antioxidant enzymes (SOD, catalase), glutathione (GSH) and related enzymes (GCL, GPx, GR, GST), and malondialdehyde (MDA) in postmortem human brain samples (n=50).
- Assessment of variations across anatomical regions: frontal cortex (FC), cerebellum (CB), medulla oblongata (MO), substantia nigra (SN), and hippocampus (HC).
- Statistical evaluation of effects related to PMI (2.5-26 h), gender, and agonal state (Glasgow Coma Scale).
Main Results:
- Superoxide dismutase (SOD) and catalase activities remained largely stable.
- Glutathione reductase (GR) and glutathione peroxidase (GPx) activities were influenced by agonal state.
- Glutathione (GSH) levels decreased with increasing PMI in the medulla oblongata (MO), correlating with increased malondialdehyde (MDA).
- Female brains exhibited higher total GSH in the cerebellum (CB) and MO compared to males.
- Hippocampus (HC) and substantia nigra (SN) showed remarkable stability for most markers.
Conclusions:
- Pre- and postmortem factors significantly affect glutathione dynamics and related enzymes in postmortem human brains, particularly in the MO.
- Antioxidant enzymes like SOD and catalase are relatively robust to these factors.
- Brain region-specific differences in marker stability have critical implications for interpreting findings in brain pathophysiology studies.
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