Uniquely Hominid Features of Adult Human Astrocytes
Open accessAbstract
Defining the microanatomic differences between the human brain and that of other mammals is key to understanding its unique computational power. Although much effort has been devoted to comparative studies of neurons, astrocytes have received far less attention. We report here that protoplasmic astrocytes in human neocortex are 2.6-fold larger in diameter and extend 10-fold more GFAP (glial fibrillary acidic protein)-positive primary processes than their rodent counterparts. In cortical slices prepared from acutely resected surgical tissue, protoplasmic astrocytes propagate Ca 2+ waves with a speed of 36 μm/s, approximately fourfold faster than rodent. Human astrocytes also transiently increase cystosolic Ca 2+ in response to glutamatergic and purinergic receptor agonists. The human neocortex also harbors several anatomically defined subclasses of astrocytes not represented in rodents. These include a population of astrocytes that reside in layers 5–6 and extend long fibers characterized by regularly spaced varicosities. Another specialized type of astrocyte, the interlaminar astrocyte, abundantly populates the superficial cortical layers and extends long processes without varicosities to cortical layers 3 and 4. Human fibrous astrocytes resemble their rodent counterpart but are larger in diameter. Thus, human cortical astrocytes are both larger, and structurally both more complex and more diverse, than those of rodents. On this basis, we posit that this astrocytic complexity has permitted the increased functional competence of the adult human brain.
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Morphological and transcriptomic comparisons have revealed prominent differences between mice and humans.
“morphological and transcriptomic comparisons have revealed prominent differences between mice and humans101–103”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [102]
The Discussion reports marked morphological differences between human and rodent astrocytes, and the Results include a direct comparison with mouse astrocytes. The paper does not report a transcriptomic comparison, so it supports the morphological part of the sentence but not the transcriptomic part. (LLM, conf=0.86)
Experimental — accuracy not yet measuredLike ILAs, VP-As do not respect the single astrocytic domain rule of neighboring astrocytes and extend processes toward long distances, without crossing layer boundaries.
“Similarly to ILAs, VP-As do not respect the single astrocytic domain rule of neighboring astrocytes and extend processes toward long distances, however without crossing the layer boundaries (Oberheim et al., 2009; Pereira and Furlan, 2010).”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Oberheim et al., 2009
The Results section on varicose projection astrocytes reports processes up to a millimeter long that frequently penetrate neighboring astrocytic domains. The Discussion says these fibers typically extend within the deep cortical layers, but does not establish that they never cross layer boundaries; it hypothesizes long-distance communication across cortical layers. (LLM, conf=0.87)
Experimental — accuracy not yet measuredVP-As are a distinct class of astrocytes positive for GFAP, with soma localized in deep layers V and VI and white matter.
“VP-As are a distinct class of astrocytes positive for GFAP, with their soma localized in the deep layers V and VI, and white matter.”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Oberheim et al., 2009
The Results section identifies varicose projection astrocytes as a distinct GFAP-positive class residing in cortical layers 5–6. It identifies fibrous astrocytes, not varicose projection astrocytes, as populating white matter; it does not support the claim that varicose projection astrocyte somata are located there. Page numbers are unavailable in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredDespite extensive studies in rodent models, the specific contributions of astrocytes to human pathology remain inadequately understood, partly due to species-specific differences.
“Despite extensive studies in rodent models, the specific contributions of astrocytes to human pathology remain inadequately understood, partly due to species-specific differences (17–20).”
From Varicose projection astrocytes: Conserved reactive cells in brain pathology (2026) · cites this paper as [17]
The Introduction says glial research has relied largely on rodent brains, and the Discussion identifies human–rodent astrocyte differences that limit rodent models of human glial biology. The Discussion’s Caveats section says the analysis describes astrocytes in tissue deemed normal; it does not establish how well astrocytes’ contributions to human pathology are understood. Page numbers are not supplied in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredVP-As are characterized by short processes around the soma and one to five long processes with varicosities spaced approximately every 10 μm along the length of the fibers.
“These cells are characterized by the presence of short processes around the soma and one to five long processes with varicosities spaced approximately every 10 μm along the length of the fibers.”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Oberheim et al., 2009
Varicose projection astrocytes are not restricted to hominoids but also appear in other mammals, like mice and tigers.
“our finding that varicose projection astrocytes are not only restricted to hominoids (17, 21) but also appear in other mammals, like mice and tigers”
From Varicose projection astrocytes: Conserved reactive cells in brain pathology (2026) · cites this paper as [17]
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“Human astrocytes are larger and structurally more complex, and synaptic islands in the human cortex are much larger than those of model animals (Oberheim et al., 2009).”
BackgroundClassical-quantum interfaces in living neural tissue supporting conscious functions
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- Authors
- Oberheim, N. A., Takano, T., Han, X., He, W., Lin, J. H. C., Wang, F., Xu, Q., Wyatt, J. D., Pilcher, W., Ojemann, J. G., Ransom, B. R., Goldman, S. A., & Nedergaard, M.
- Affiliations
- University of Rochester Medicine (US)
- New York Medical College (US)
- University of Washington (US)
- Corresponding author
- Nedergaard, Maiken
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-03-11
- Volume
- 29
- Issue
- 10
- Pages
- 3276-3287
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2819812
- OpenAlex
- W1971125401
- Cited by
- 1,488
- References
- 1
- Citations by year
- 2026: 66 · 2025: 113 · 2024: 124 · 2023: 139 · 2022: 135 · 2021: 156 · 2020: 100 · 2019: 90 · 2018: 72 · 2017: 81 · 2016: 103 · 2015: 68 · 2014: 54 · 2013: 52 · 2012: 41
- FWCI
- 18.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS015589)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- human astrocytes, protoplasmic astrocyte, human neocortex, calcium wave propagation, fibrous astrocytes, human brain evolution
- MeSH terms
- Adolescent, Adult, Aged, Animals, Astrocytes, Child, Child, Preschool, Pan troglodytes, Humans, Macaca mulatta, Middle Aged, Saimiri, Species Specificity, Hominidae, Rats, Sprague-Dawley, Mice, Rats, Young Adult
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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