AGE-DEPENDENT CHANGES IN THE IMMUNOREACTIVITY FOR NEUROFILAMENTS IN RABBIT HIPPOCAMPUS

The distribution of the three subunits of neurofilaments was examined in the hippocampus of young adult rabbits (three months of age), emplo ying a panel of six monoclonal antibodies. Thereafter, age-dependent a nd subunit-selective changes in neurofilament immunoreactivity in the ageing rabbit hippocampus were studied, using animals of one, three, s ix, 12, 24, 30, 36, 48, and 60 months. Principal cells, interneurons, axons, and various fibre systems were immunoreactive for all three sub units, although the localization and staining intensity of neurofilame nt immunoreactivity depended on the antibody used. Small cells immunop ositive for the low subunit of neurofilament (presumably glial cells) were found abundantly in the hippocampal formation al one month, and ( occasionally) at 30-36 months. Young rabbits (one to three months of a ge) had high numbers of interneurons stained for the high subunit of n eurofilament in the stratum oriens/pyramidale. The number declined and plateaued to approximately 78% at six to 30 months, and further decli ned and plateaued to approximately 56% at 36-60 months. The first decl ine may reflect a process of maturation, while the latter decline most likely relates to ageing. Ageing pyramidal cells in 48-60 months anim als revealed a slight increase for the low subunit of neurofilament, b ut no changes for the other subunits. Transient changes in neurofilame nt immunoreactivity were a striking observation in dentate gyrus granu le cells during ageing. The staining intensity for the low subunit of neurofilament decreased gradually from one to 24-30 months until it wa s no longer detectable in these cells. The immunoreactivity then reapp eared. most notably in granule cells lining the hilus, at the age of 3 6-48 months. By 60 months all granule cells were nearly immunonegative for this subunit. Axonal aberrations, immunoreactive for all three su bunits, were found throughout the hippocampal formation. These aberrat ions first appeared in 24-month-old animals and increased in number an d maximal size in older rabbits. The alterations in neurofilament immu noreactivity in the ageing hippocampus correlated with age-associated learning disabilities in the acquisition of a hippocampally-dependent learning task. The potential relevance of changes in the cytoskeletal profile of hippocampal neurons to age-associated learning and memory d isabilities is discussed. (C) 1997 IBRO.