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), employing a panel of six monoclonal antibodies. Thereafter, age-dependent and subunit-selective changes in neurofilament immunoreactivity in the ageing rabbit hippocampus were studied, using animals of one, three, six, 12, 24, 30, 36, 48, and 60 months. Principal cells, interneurons, axons, and various fibre systems were immunoreactive for all three subunits, although the localization and staining intensity of neurofilament immunoreactivity depended on the antibody used. Small cells immunopositive for the low subunit of neurofilament (presumably glial cells) were found abundantly in the hippocampal formation at one month, and (occasionally) at 30-36 months. Young rabbits (one to three months of age) had high numbers of interneurons stained for the high subunit of neurofilament in the stratum oriens/pyramidale. The number declined and plateaued to approximately 78% at six to 30 months, and further declined and plateaued to approximately 56% at 36-60 months. The first decline may reflect a process of maturation, while the latter decline most likely relates to ageing. Ageing pyramidal cells in 48-60 months animals revealed a slight increase for the low subunit of neurofilament, but no changes for the other subunits. Transient changes in neurofilament immunoreactivity were a striking observation in dentate gyrus granule cells during ageing. The staining intensity for the low subunit of neurofilament decreased gradually from one to 24-30 months until it was no longer detectable in these cells. The immunoreactivity then reappeared, most notably in granule cells lining the hilus, at the age of 36-48 months. By 60 months all granule cells were nearly immunonegative for this subunit. Axonal aberrations, immunoreactive for all three subunits, were found throughout the hippocampal formation. These aberrations first appeared in 24-month-old animals and increased in number and maximal size in older rabbits. The alterations in neurofilament immunoreactivity 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 disabilities is discussed.