EXPRESSION OF TERMININ, A SENESCENCE-RELATED CYTOPLASMIC PROTEIN, IN THE AGING RAT-BRAIN

Terminin is a cytoplasmic protein expressed in irreversibly growth-arr ested senescent fibroblast cultures and in terminally differentiated c ells of various epithelia. In the present study, terminin was identifi ed by immunohistochemistry in the cytoplasm of neurons and glia of agi ng rat brain using the monoclonal antibody (Mab) 1.2. Few terminin-pos itive neurons were observed in 3-month-old brain. At 18 months, termin in immunoreactivity was noted in dentate gyrus granule cells, in hippo campal fibre projections and in neuronal perikarya of deep cerebellar nuclei (but not in cerebellar cortex). In 33-month brain, terminin imm unoreactivity in the dentate gyrus was more intense than at 18 months but immunoreactive fibre bundles in the hippocampus were no longer see n. At 33 months, the cerebellar granule cell layer contained terminin- positive horizontal interneurons and received immunoreactive axonal pr ojections not seen in the younger preparations. In addition, ubiquitou s low-level terminin expression was noted in neurons of the cerebral c ortex, hippocampus and cerebellum of the 33-month-old animals. Thus, i n the rat CNS, an increase in terminin appears to be a physiologic mar ker of neuronal aging. Small numbers of terminin-positive neuroglia we re present in gray and white matter of 3-month-old brain and became in creasingly more abundant in the 18- and 33-month-old animals. However, even in senescent brains, terminin-positive neuroglia represented a v ery small fraction of the entire glial pool. Terminin expression in sl owly renewing neuroglial populations may identify those cells in which degeneration and death are imminent. Immunoblots of insoluble fractio ns of aging brain homogenates using the 1.2 Mab revealed the absence o f the 90-kDa form of terminin in 3-month-old preparations. At this tim e point, only the 60-kDa form of terminin was detected. At 18 and 33 m onths, increases in the intensity of the 90- and 60-kDa bands were see n. In soluble fractions of 3-month-old brain, a single 90-kDa terminin band was observed which intensified at 18 and 33 months. Our results indicate that terminin immunoreactivity in rat brain sections increase s with aging and correlates with the amount of 90- and 60-kDa terminin peptides assayed by Western blotting.