BACKGROUND & OBJECTIVES: Rising prevalence of neurodegenerative disorders with a steady increase in aged-population necessitates studies of the human brain to understand their pathophysiology. As animal models are not available, medical centers have established "brain banks" to provide autopsy brain samples for such research. Frozen tissues must be of optimal quality to permit molecular and protein studies. Post-mortem interval (PMI) is an important factor affecting tissue quality although its effects on brain physiology are unclear. We undertook this study to analyze the biochemical effects of PMI on protein stability in human brains collected at autopsy and stored at the brain bank of a tertiary care neurosciences institute in south India. METHODS: Different neuroanatomical areas including frontal cortex (FC), cerebellum (CB), caudate nucleus (CD) and substantia nigra (SN) from autopsy human brains (n=9) with varying PMI (4-18 h) were analyzed for pH, protein insolubility, protein oxidation/ nitration and protein expression of glial fibrillary acidic protein (GFAP), synatophysin and neurofilament (NF). Histological changes at different PMI were also assessed. RESULTS: An increase in tissue pH was noted with increasing PMI. Although there was no significant alteration in solubility of proteins, SN showed increased protein oxidation/nitration events, GFAP and NF expression with increasing PMI. No major abnormalities in cell morphology or tissue integrity were noted. Immunohistochemistry with GFAP and NF did not show any significant increase in signal in FC at high PMI. INTERPRETATION & CONCLUSION: In post-mortem human brains, although there were no gross structural changes at the tissue level with increasing PMI, biochemical events such as oxidative and nitrosative damage of cellular proteins, tissue pH could be considered as markers of tissue quality for biochemical research. Further, SN was found to be most susceptible to PMI related changes.
BACKGROUND & OBJECTIVES: Rising prevalence of neurodegenerative disorders with a steady increase in aged-population necessitates studies of the human brain to understand their pathophysiology. As animal models are not available, medical centers have established "brain banks" to provide autopsy brain samples for such research. Frozen tissues must be of optimal quality to permit molecular and protein studies. Post-mortem interval (PMI) is an important factor affecting tissue quality although its effects on brain physiology are unclear. We undertook this study to analyze the biochemical effects of PMI on protein stability in human brains collected at autopsy and stored at the brain bank of a tertiary care neurosciences institute in south India. METHODS: Different neuroanatomical areas including frontal cortex (FC), cerebellum (CB), caudate nucleus (CD) and substantia nigra (SN) from autopsy human brains (n=9) with varying PMI (4-18 h) were analyzed for pH, protein insolubility, protein oxidation/ nitration and protein expression of glial fibrillary acidic protein (GFAP), synatophysin and neurofilament (NF). Histological changes at different PMI were also assessed. RESULTS: An increase in tissue pH was noted with increasing PMI. Although there was no significant alteration in solubility of proteins, SN showed increased protein oxidation/nitration events, GFAP and NF expression with increasing PMI. No major abnormalities in cell morphology or tissue integrity were noted. Immunohistochemistry with GFAP and NF did not show any significant increase in signal in FC at high PMI. INTERPRETATION & CONCLUSION: In post-mortem human brains, although there were no gross structural changes at the tissue level with increasing PMI, biochemical events such as oxidative and nitrosative damage of cellular proteins, tissue pH could be considered as markers of tissue quality for biochemical research. Further, SN was found to be most susceptible to PMI related changes.
Authors: Fabio Di Domenico; Gilda Pupo; Cesare Mancuso; Eugenio Barone; Francesca Paolini; Andrea Arena; Carla Blarzino; Frederick A Schmitt; Elizabeth Head; D Allan Butterfield; Marzia Perluigi Journal: J Alzheimers Dis Date: 2015 Impact factor: 4.472
Authors: Rajeswara Babu Mythri; C Venkateshappa; G Harish; Anita Mahadevan; Uday B Muthane; T C Yasha; M M Srinivas Bharath; S K Shankar Journal: Neurochem Res Date: 2011-04-12 Impact factor: 3.996
Authors: C Venkateshappa; G Harish; Rajeswara Babu Mythri; Anita Mahadevan; M M Srinivas Bharath; S K Shankar Journal: Neurochem Res Date: 2011-10-05 Impact factor: 3.996
Authors: Robert E McCullumsmith; John H Hammond; Dan Shan; James H Meador-Woodruff Journal: Neuropsychopharmacology Date: 2013-10-04 Impact factor: 7.853
Authors: William D Dunn; Marla Gearing; Yuna Park; Lifan Zhang; John Hanfelt; Jonathan D Glass; David A Gutman Journal: Neuropathology Date: 2015-11-18 Impact factor: 1.906