PERIKARYAL ACCUMULATION AND PROTEOLYSIS OF NEUROFILAMENT PROTEINS IN THE POSTMORTEM RAT-BRAIN

Investigations of neurofilament alterations in neurodegenerative disor ders utilize postmortem human tissues obtained at autopsy. To determin e if alterations in the levels or distribution of neurofilament protei ns might occur during the interval between death and autopsy, the post mortem cooling curve of the human brain was modeled in Sprague-Dawley rats and neurofilament proteins were examined by immunocytochemistry a nd immunoblots. One hour after death, enhanced perikaryal immunostaini ng of NF-M and both phosphorylated and nonphosphorylated NF-H epitopes was observed throughout the hippocampal formation. A greater number o f neurons exhibited increased somatic immunostaining 4-h postmortem. I n addition, loss of neurofilament protein immunostaining was observed in the neuropil, particularly in the molecular layer of the dentate gy rus. This corresponded with, but lagged behind, the pattern of calpain activation determined using an antibody against calpain-cleaved alpha -spectrin. Immunoblots confirmed the postmortem loss of neurofilament proteins in both triton-soluble and insoluble fractions. These results demonstrate that the levels and localization of neurofilament protein s observed in tissues obtained at autopsy even with short postmortem i ntervals may not accurately reflect the premortem condition.