ATTENUATION OF FOS-LIKE IMMUNOREACTIVITY INDUCED BY A SINGLE ELECTROCONVULSIVE SHOCK IN BRAINS OF AGING MICE

c-fos is a proto-oncogene that encodes for a nuclear phosphoprotein with DNA binding properties and is presumed to have an important role in the long-term regulation of neuronal function. It is thought to act as a 'third messenger' molecule in signal transduction systems and its expression has been shown to be induced by a variety of exogenous and endogenous stimuli. This study examines the differential expression of the Fos protein in various brain regions after a single electroconvulsive shock (ECS) in 6-, 13-, and 28-month-old B6C3 mice. The animals received an acute electroconvulsive shock (90 V for 0.3 s), without prior anesthesia, through earclip electrodes and exhibited generalized tonic-clonic seizures lasting 20-36 s. Animals were anesthetized and perfused intracardially with 2.5% acrolein, 4% paraformaldehyde at 0.5, 1.0, 2.0 and 4.0 h postshock. The brains were Vibratome-sectioned (30-mu-m) and examined using a Fos antibody, directed against a conserved region of both mouse and human Fos by standard immunocytochemical methods. Systematic sampling of the total number of Fos immunostained neurons in amygdala, hippocampus and the cerebral cortex showed peak values at the 1-h time point followed by a steady decline thereafter in all age groups. In a second experiment, Fos-like immunoreactivity was compared 1 h after ECS in the hippocampus, amygdala and the cortex in all 3 age groups. There was increased expression of Fos-like immunoreactivity after ECS- compared to non-ECS-treated controls in all age groups. Compared to the young animals, the mid-age group exhibited a 40-46% decrease in amygdala and cortical areas, respectively, and no significant difference in the hippocampus. However in old animals, Fos-like immunoreactivity was reduced between 58 and 62% in all brain regions examined. These results demonstrate that: (1) Fos is expressed rapidly and transiently in response to ECS in animals of all ages; and (2) there is a decline in Fos-like immunoreactivity in brains of aging animals. We conclude that Fos expression is compromised in the brains of aging animals and these changes may be part of a cascade of events that lead to functional impairments and possibly a reduction in neuronal viability with age.