A Sequential Study of Age-Related Lipofuscin Accumulation in Hippocampus and Striate Cortex of Rats

Abstract

Background: The age-pigment, lipofuscin that accumulates in cells intrinsically and progressively with age is considered as the hallmark of aging. This accumulation is more prominent in post-mitotic cells like neurons and also appears in glia. Purpose: The aim of the present study was to assess the age-associated occurrence and distribution pattern of lipofuscin both in neurons and microglia in various regions of hippocampus and striate cortex. Methods: The accumulation pattern of lipofuscin in hippocampus and striate cortex was observed in the female Wistar rats of 6 age groups, that is, 3, 6, 12, 18, 24, and 30 months using the autofluorescent property of lipofuscin and its specific localization in neurons and microglia by dual immunolabeling with NeuN and Iba-1 antibodies respectively. Cytoarchitectural and the morphological age-related changes were observed with cresyl violet staining. Results: Lipofuscin pigments accumulate progressively through the normal aging process in hippocampus and striate cortex. However, in hippocampus, lipofuscin accumulates in a region-specific manner with the highest accumulation observed in cornu ammonis (CA) 1 and 3 subregions. Furthermore, the lipofuscin accumulation was also observed in microglia in the senile brains both in the hippocampus and striate cortex. Conclusion: The progressive deposition of lipofuscin could result in cellular dysfunction. This encouraged us to forward the idea that microglia not only participate in the removal of the pigment from the neurons but also accumulate these waste products in itself. Such senescent microglia may contribute to age- related neurodegeneration as they lose the neuroprotective potential due to oxidative stress and thus may be unable to effectively phagocytose the age pigment.