Calpain proteolysis of αll-spectrin in the normal adult human brain

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