Immunocytochemical study on the distribution of p53 in the hippocampus andcerebellum of the aged rat

A role for p53-mediated modulation of neuronal viability has been suggested by the finding that p53 expression is increased in damaged neurons in mode ls of ischemia and epilepsy. P53 gene upregulation precedes apoptosis in ma ny cell types, and a potential role for this molecule in apoptosis of neuro ns has already been demonstrated in Alzheimer's disease. Recent studies sug gest that p53-associated apoptosis may be a common mechanism of cell loss i n several important neurodegenerative diseases. In the present study, we ex amined changes in p53-immunoreactive (IR) neurons in the brains of aged rat s for the first time employing immunocytochemical and in situ hybridization methods. P53-IR neurons were found in the CAI region of hippocampus, septa l region and cerebellum in the aged rats, but there was no p53-TR cell in t he brains of adult rats. In the hippocampus of the aged rat, p53-IR cells p redominated in the stratum oriens and pyramidal layers, while the molecular layer contained relatively few p53-IR cells. The most prominent population of immunoreactive labeling in cerebellar cortex was localised within the c ell bodies of Purkinje cells and dendrites in molecular layers. Upregulatio n of p53 in the Purkinje cells observed in this study suggests that signifi cant loss of Purkinje cells with aging may be regulated with several apopto sis-controlling factors including p53 and oxidative stress mechanism. Furth er investigations are required to establish whether direct functional relat ions exist between p53 and the apoptotic neuronal death in normal aging or Alzheimer brains. (C) 2000 Elsevier Science B.V. All rights reserved.