Expression of terminin, a senescence-related cytoplasmic protein, in the aging rat brain

Terminin is a cytoplasmic protein expressed in irreversibly growth-arrested senescent fibroblast cultures and in terminally differentiated cells of various epithelia. In the present study, terminin was identified by immunohistochemistry in the cytoplasm of neurons and glia of aging rat brain using the monoclonal antibody (Mab) 1.2. Few terminin-positive neurons were observed in 3-month-old brain. At 18 months, terminin immunoreactivity was noted in dentate gyrus granule cells, in hippocampal fibre projections and in neuronal perikarya of deep cerebellar nuclei (but not in cerebellar cortex). In 33-month brain, terminin immunoreactivity in the dentate gyrus was more intense than at 18 months but immunoreactive fibre bundles in the hippocampus were no longer seen. At 33 months, the cerebellar granule cell layer contained terminin-positive horizontal interneurons and received immunoreactive axonal projections not seen in the younger preparations. In addition, ubiquitous low-level terminin expression was noted in neurons of the cerebral cortex, hippocampus and cerebellum of the 33-month-old animals. Thus, in the rat CNS, an increase in terminin appears to be a physiologic marker of neuronal aging. Small numbers of terminin-positive neuroglia were present in gray and white matter of 3-month-old brain and became increasingly more abundant in the 18- and 33-month-old animals. However, even in senescent brains, terminin-positive neuroglia represented a very small fraction of the entire glial pool. Terminin expression in slowly renewing neuroglial populations may identify those cells in which degeneration and death are imminent.(ABSTRACT TRUNCATED AT 250 WORDS)