Cited by 84Neuroscience and Neuropharmacology ResearchBarrier Structure and Function StudiesNeuroinflammation and Neurodegeneration Mechanisms

Cortical interlaminar astrocytes across the therian mammal radiation.

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Falcone, Carmen, Wolf‐Ochoa, Marisol, Amina, Sarwat, Hong, Tiffany, Vakilzadeh, Gelareh, Hopkins, William D., Hof, Patrick R., Sherwood, Chet C. +3 more·2019·Journal of Comparative Neurology

Abstract

Interlaminar astrocytes (ILA) in the cerebral cortex possess a soma in layer I and extend an interlaminar process that runs perpendicular to the pia into deeper cortical layers. We examined cerebral cortex from 46 species that encompassed most orders of therian mammalians, including 22 primate species. We described two distinct cell types with interlaminar processes that have been referred to as ILA, that we termed pial ILA and supial ILA. ILA subtypes differ in somatic morphology, position in layer I, and presence across species. We further described rudimentary ILA that have short GFAP + processes that do not exit layer I, and “typical” ILA with longer GFAP + processes that exit layer I. Pial ILA were present in all mammalian species analyzed, with typical ILA observed in Primates, Scandentia, Chiroptera, Carnivora, Artiodactyla, Hyracoidea, and Proboscidea. Subpial ILA were absent in Marsupialia, and typical subpial ILA were only found in Primate. We focused on the properties of pial ILA by investigating the molecular properties of pial ILA and confirming their astrocytic nature. We found that while the density of pial ILA somata only varied slightly, the complexity of ILA processes varied greatly across species. Primates, specifically bonobo, chimpanzee, orangutan, and human, exhibited pial ILA with the highest complexity. We showed that interlaminar processes contact neurons, pia, and capillaries, suggesting a potential role for ILA in the blood–brain barrier and facilitating communication among cortical neurons, astrocytes, capillaries, meninges, and cerebrospinal fluid.

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Crossref · 10.1002/cne.24605

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  • ILAs are characterized by one or more long processes that may enter the deeper cortex, take a diagonal or tangential direction, remain in the superficial laminae, or not exit their cortical layer.

    “ILAs are characterized by one or more long processes that may enter the deeper cortex, take a diagonal or tangential direction, remain in the superficial laminae, or even not exit their cortical layer”

    From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Falcone et al., 2019

    The Results sections report interlaminar processes that descend into deeper layers, sometimes at an oblique angle, and rudimentary ILA whose processes do not leave layer I (page not provided). However, the layer-I-confined processes of rudimentary ILA are described as short, not long. The authors also say they did not observe the superficial tangential fiber system described in earlier work, so the tangential-direction part is not supported by their observations. (LLM, conf=0.84)

    Experimental — accuracy not yet measured
  • ILA processes contact MAP2+ neuronal processes in postmortem rhesus macaque brains.

    “ILA processes have been shown to contact MAP2+ neuronal processes (Falcone et al., 2019) in postmortem rhesus macaque brains”

    From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Falcone et al., 2019

    The Results section ('ILA contact capillaries and neuronal processes'; page not provided) reports that MAP2+ neuronal processes contacted GFAP+ ILA processes in rhesus macaque cortical tissue. The Materials and Methods ('Tissue processing'; page not provided) says the rhesus macaques were sacrificed and intracardially perfused, distinguishing them from specimens collected postmortem. The contact finding is supported, but the postmortem-specimen description is not. (LLM, conf=0.87)

    Experimental — accuracy not yet measured
  • ILAs are present in all mammals, albeit with pronounced morphological differences.

    “more recent studies demonstrated that ILAs are present in all mammals, albeit with pronounced morphological differences”

    From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Falcone et al., 2019

    The Results section ('All therian mammals investigated present typical, or rudimentary, ILA'; page unavailable) reports ILAs in the therian mammals studied and describes differences in process length and complexity. The claim extends that finding to all mammals, which the paper does not establish. (LLM, conf=0.88)

    Experimental — accuracy not yet measured
  • ILA membranes express high levels of Aqp4 marker, including around the cell body which is in strict contact with the pia surface.

    “ILA membranes have been shown to express high levels of Aqp4 marker, also around the cell body which is in strict contact with the pia surface (Falcone et al., 2019).”

    From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Falcone et al., 2019

    The Results (Molecular characterization of ILA; page unavailable) report AQP4 expression in rhesus-monkey pial ILA, and the Discussion (Pial ILA distribution; page unavailable) says their cell-body bases contact the pia. The copy does not establish high AQP4 levels or specifically locate AQP4 on membranes around the cell body. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • Club-endings of ILA processes are closely related to neurons.

    “Double labeling of GFAP and Map2 or GFAP and SMI311 (for the IV intermediate filament of the neuronal cytoskeleton) revealed a close relation between the club-ending and neurons”

    From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Falcone et al., 2019

    The Results section, “ILA contact capillaries and neuronal processes” (page unavailable), reports that MAP2-positive neuronal processes contacted GFAP-positive ILA processes. A separate Results passage describes bulbous process endings, but does not establish that those endings specifically contacted neurons. Our copy also does not substantiate the claimed GFAP–SMI311 double labeling. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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Authors
Falcone, C., Wolf‐Ochoa, M., Amina, S., Hong, T., Vakilzadeh, G., Hopkins, W. D., Hof, P. R., Sherwood, C. C., Manger, P. R., Noctor, S. C., & Martínez‐Cerdeño, V.
Affiliations
  • Shriners Hospitals for Children - Northern California (US)
  • Georgia State University (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • George Washington University (US)
  • University of the Witwatersrand (ZA)
  • University of California Davis Medical Center (US)
Corresponding author
Martínez‐Cerdeño, Verónica
Venue
Journal of Comparative Neurology
Publisher
Wiley
Published
2019-01-25
Volume
527
Issue
10
Pages
1654-1674
ISSN
  • 0021-9967 (ISSN-L)
  • 1096-9861
OpenAlex
W2903748606
Cited by
84
References
7
Citations by year
2026: 15 · 2025: 16 · 2024: 16 · 2023: 15 · 2022: 9 · 2021: 5 · 2020: 5 · 2019: 2 · 2018: 1
FWCI
1.48
Type
journal article
Language
en
Open access
Locations
  • The Journal of Comparative Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • SDL (submittedVersion)
Funders
Shriners Hospitals for Children
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
cerebral cortex, therian mammals, primate cerebral cortex, glial fibrillary acidic protein, blood-brain barrier, meninges, cerebrospinal fluid, astrocyte morphology, marsupials
MeSH terms
Animals, Astrocytes, Cerebral Cortex, Mammals

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