The proteolysis of all-spectrin by calpain may be physiologically involved
with synaptic remodeling, long-term potentiation, and memory formation. Cal
pain activation may also mediate neuronal apoptosis, responses to hypoxic i
nsult, and excitotoxic injury. Surprisingly little is known of the activity
of these calpain-mediated processes in the adult human brain. Using an ant
ibody that specifically recognizes calpain-cleaved all-spectrin, we have ma
pped the topographic distribution of the major alpha II-spectrin break-down
product (alpha II-bdp1) in six adult brains examined post-mortem. All brai
ns were from patients without evident neurological disease. Focally positiv
e alpha II-bdp1 was consistently detected in the neuropil of the cortical g
ray matter, in occasional pyramidal neurons, and in rare reactive astrocyte
s in the cerebral cortex and hippocampus. Cerebellar Purkinje cells were mo
re frequently, and more intensely, immunopositive. In all fields, staining
was most intense in the soma and dendrites of neurons. There was no correla
tion of the frequency of positive cells with the postmortem interval or cli
nical condition. While these findings do not rigorously exclude contributio
ns from postmortem calpain activation, they do suggest that a low-level of
calpain processing of all-spectrin is likely to be a constitutive process i
n the adult human brain. (C) 2001 Elsevier Science Ireland Ltd. All rights
reserved.