Expression of statin, a non-proliferation-dependent nuclear protein, in the postnatal rat brain: evidence for substantial retention of neuroglial proliferative capacity with aging.
Statin is a 57 kDa protein expressed in nuclei of reversibly and irreversibly growth-arrested (Go-phase) cells. In this report, immunohistochemical localization of statin in the developing and aging rat brain was achieved using the monoclonal antibody, S-44. On postnatal day 2, post-migratory neurons in the developing cerebral cortex were statin-positive. Many statin-negative cells were observed in the lateral subependymal zone of the lateral ventricle. By postnatal day 10, most neuronal nuclei were statin-positive although small numbers of statin-negative neurons were still encountered in the lateral subependymal zone and hippocampal dentate gyrus. At 3, 18 and 33 months, all neuronal nuclei surveyed were statin-positive. These results support the contention that, save for the postnatal persistence of 'germinal zones' such as the subependymal region and dentate gyrus, neuronal proliferation in the rat is largely completed by the time of birth. In striking contrast to neuronal statin expression, a significant fraction of neuroglia in both grey and white matter remains statin-negative at all ages examined. In the corpus callosum, 33.2%, 34.0% and 34.7% of glial nuclei were statin-negative at 3, 18 and 33 months, respectively. These findings indicate that: (i) even in senescent brain, the cycling (statin-negative) glial pool is substantially larger than previously surmised from S-phase labeling experiments; and (ii) during aging, the ratio of noncycling-to-cycling neuroglia remains very tightly regulated. Examination of other non-neuronal cell types revealed that most, if not all, ependymal and choroid plexus epithelial cells were statin-positive in the neonatal and adult brains in keeping with the predominantly prenatal proliferation of these tissues. Our results indicate that statin immunolabeling using the S-44 antibody is a powerful technique for the in situ identification of non-proliferating cells in the developing and aging nervous system.
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