Redefining varicose projection astrocytes in primates

Abstract

Varicose projection astrocytes (VP-As) are found in the cerebral cortex and have been described to be specific to humans and chimpanzees. To further examine the phylogenetic distribution of this cell type, we analyzed cortical tissue from several primates ranging from primitive primates to primates evolutionary closer to human such as apes. We specifically analyzed tissue from four strepsirrhine species, one tarsier, six species of platyrrhine monkeys, ten species of cercopithecoid monkeys, two hylobatid ape species, four to six cases each of chimpanzee, bonobo, gorilla, and orangutan, and thirteen human. We found that VP-As were present only in human and other apes (hominoids) and were absent in all other species. We showed that VP-As are localized to layer VI and the superficial white matter of the cortex. The presence of VP-As co-occured with interlaminar astrocytes that also had varicosities in their processes. Due to their location, their long tangential processes, and their irregular presence within species, we propose that VP-As are astrocytes that develop varicosities under specific conditions and that are not a distinct astrocyte type.

Glial Patchwork: Oligodendrocyte Progenitor Cells and Astrocytes Blanket the Central Nervous System

“…Astrocyte territory size is affected in models of other diseases such as Huntington’s disease (Zhou et al, 2019 ), though it is unclear if this affects tiling mechanisms or if it is only a morphological defect. It has also been proposed that human varicose projection astrocytes, which send projections into the territories of other astrocytes, may not be their own subtype but instead are astrocytes in a certain unknown state, either developmental or pathological (Falcone et al, 2022 ). Unfortunately, there is little information on the effects of disease on tiling itself or if perturbations to tiling may underlie the etiology of nervous system disorders.…”

Evolution of astrocytes: From invertebrates to vertebrates

“…Astrocytes as we know them today have been mostly investigated in mammals, and more specifically in the mouse, in humans, and in non-human primates. Although scarce, studies in different mammalian species point to great astrocyte heterogeneity across mammals, with specific astrocyte morphology, density, and functions in primates ( Oberheim et al, 2009 ; Verkhratsky et al, 2018 ; Falcone et al, 2019 ; 2021 ).…”

“…Scale bar = 10 μm. (F,F′) Adapted from Falcone et al, 2021 , Figure 2C . GFAP + VP-A in frontal cortex of a gorilla.…”

Fate mapping of neural stem cell niches reveals distinct origins of human cortical astrocytes

“…Our study also implicates truncated radial glia ( 3 ), which have not been described in mice, in the generation of a distinct subtype of cortical “dense bulbous” astrocytes that have been previously observed in humans ( 20 , 28 ), but not in rodents. Additional studies are needed to determine the developmental origin of other astrocyte subtypes thought to be enriched in humans, such as varicose projection and interlaminar astrocytes ( 29 , 30 ).…”