Demonstration of puromycin-sensitive alanyl aminopeptidase in Alzheimer disease brain.

Puromycin-sensitive alanyl aminopeptidase (PSA, EC 3.4.11.14) is a member of the ubiquitous aminopeptidase family, which cleaves N-terminal amino acids from proteins. PSA is suggested to function as a trimming protease in the MHC class I pathway, which is activated in brains of Alzheimer disease (AD). We examined the immunohistochemical localization of PSA in brains of AD and control cases using a rabbit anti-PSA. In the control cases, the antiserum revealed staining in a few glial cells and blood vessels. In AD brain, however, intensely stained cells were found richly in the cerebral cortex. Double immunofluorescence studies confirmed that PSA-positive cells were reactive microglia. Such PSA-positive reactive microglia tended to locate in and around senile plaques and were sometimes observed to associate with neurons containing neurofibillary tangles. The present result indicates that reactive microglia express PSA-immunoreactive molecules, probably in association with the pathological conditions of AD.

Morphologic study of neuronal death, glial activation, and progenitor cell division in the hippocampus of rat models of epilepsy.

PURPOSE: To clarify the relationship of neuronal death to cellular responses, we studied neuronal death as well as reactions of glia and progenitor cells in the hippocampus of two rat models of epilepsy. METHODS: Seizures were induced by either kainic acid (KA) administration or electrical kindling. Neuronal degeneration was assessed by in situ DNA fragmentation analysis. Reactions of glial cells were studied by immunohistochemistry. Progenitor cell division was evaluated using the bromodeoxyuridine (BrdU) labeling method. RESULTS: DNA fragmentation and reactive microglia were observed in the CA1, CA3, and hilus region for 24 h to 4 weeks after KA injection, but not detected in the kindling model. Reactive astrocytes and enhancement of progenitor cell division were seen in both animal models. The number of BrdU-positive cells began to increase on day 3 after KA injection, peaked on day 5, and returned to baseline on day 10. After kindling, the number of BrdU-positive cells began to increase after five consecutive experience of stage I seizures. CONCLUSIONS: These observations show that neuronal degeneration is not necessary for triggering the upregulation. Microglial activation is closely related to the neuronal death process induced by KA.