Jw. Geddes et al., PERIKARYAL ACCUMULATION AND PROTEOLYSIS OF NEUROFILAMENT PROTEINS IN THE POSTMORTEM RAT-BRAIN, Neurobiology of aging, 16(4), 1995, pp. 651-660
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.