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.

Age‐related behavioral and ultrastructural changes in the rat amygdala

“…In regard to ultrastructural changes, our observation of moderate lipopigment aggregates, moderate changes in lysosomal hydrolytic activity and protein import apparatus, as well as activation of glia detected in aged rats are compatible with other reported observations and may reflect an increased dysfunction of the cellular machinery impeding the clearance of damaged organelles (Abbruzzese et al., 2019; Grune et al., 2004; Kushwaha et al., 2018). In this regard, increased lipofuscin concentrations, glial activation, free radical formation, and protein aggregates are considered the hallmarks of age‐related neurodegenerative disorders (Moreno‐García et al., 2018; Reeg & Grune, 2015).…”

The Role of Microglia and the Nlrp3 Inflammasome in Alzheimer's Disease

“…For example, aging microglia exhibit altered cytokine production, making microglial cells more susceptible to adopting a pro-inflammatory state that also primes the cells for inflammasome activation (56,57). Aging microglial cells also have an increased accumulation of lipofuschin that has been associated with increased oxidative stress, which may cause microglia to lose their neuroprotective potential and contribute to age-related pathology (58,59). Additional evidence suggests that components of the inflammasome including caspase-1, caspase-11, Asc, and IL-1β are increased in the cytosolic fraction of hippocampal lysates in aged mice, suggesting that inflammasome formation contributes to inflammation in aging (60).…”

The search for a unique Raman signature of amyloid-beta plaques in human brain tissue from Alzheimer's disease patients

“…Lipofuscin is also known to "accumulate progressively through the normal aging process in hippocampus", in humans and in animals. [56][57][58][59][60] Its broad fluorescence is also known from retinal imaging in humans 61 and was described as fluorescence source by Chen et al, using two-photon fluorescence on live transgenic mice brain tissue. 62,63 The tiny lipofuscin granulates, usually 0.1 to 5 µm in size, 53,64 accumulate to deposits and fill the cytoplasm of cells, therefore reaching a size of 10 to 20 µm.…”

“…71 Further, lipofuscin was also found next to microglia, 52 in mice and rat brain tissue. 56,62 Plaque locations A third component of the manual segmentation are the spectra of confirmed plaque locations. The location of plaques and hence their spectra is only known from the fluorescence image of the Thioflavin-S stained tissue.…”