Astrocytic complexity distinguishes the human brain
Abstract
One of the most distinguishing features of the adult human brain is the complexity and diversity of its cortical astrocytes. Human protoplasmic astrocytes manifest a threefold larger diameter and have tenfold more primary processes than those of rodents. In all mammals, protoplasmic astrocytes are organized into spatially non-overlapping domains that encompass both neurons and vasculature. Yet unique to humans and primates are additional populations of layer 1 interlaminar astrocytes that extend long (millimeter) fibers, and layer 5-6 polarized astrocytes that also project distinctive long processes. We propose that human cortical evolution has been accompanied by increasing complexity in the form and function of astrocytes, which reflects an expansion of their functional roles in synaptic modulation and cortical circuitry.
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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 [103]
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 Oberheim et al., 2006
Astrocytes are directly involved in synaptic connections and control, ranging from ionic balance to the genesis and behavior of synapses.
“Evidence now shows that astrocytes are directly involved in synaptic connections and control, ranging from ionic balance to the genesis and behavior of synapses”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Oberheim et al., 2006
Typical human astrocytes display a radial stellate morphology.
“Typical human astrocytes display a radial stellate morphology [38, 108]”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [108]
Major differences in glial structure and function between human and mice have been described.
“major differences in glial structure and function between human and mice have been described38”
From Canonical genetic signatures of the adult human brain (2015) · cites this paper as [38]
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Koch, G., Di Lorenzo, F., Loizzo, S., Motta, C., Travaglione, S., Baiula, M., Rimondini, R., Ponzo, V., Bonnì, S., Toniolo, S., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-14204-3 · Cited by 64 · see citing works
Redefining varicose projection astrocytes in primates.
Falcone, C., McBride, E. L., Hopkins, W. D., Hof, P. R., Manger, P. R., Sherwood, C. C., Noctor, S. C., & Martínez‐Cerdeño, V. (2022) · Glia · doi:10.1002/glia.24093 · Cited by 56 · see citing works
Calcium-Sensing Receptors of Human Neural Cells Play Crucial Roles in Alzheimer's Disease
Chiarini, A., Armato, U., Liu, D., & Dal Prà, I. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00134 · Cited by 51 · see citing works
Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders
Kaminsky, N., Bihari, O., Kanner, S., & Barzilai, A. (2016) · Genomics, Proteomics & Bioinformatics · doi:10.1016/j.gpb.2016.04.003 · Cited by 38 · see citing works
Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain
Ciani, C., & Falcone, C. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1477753 · Cited by 11 · see citing works
Henao‐Restrepo, J., López‐Murillo, C., Valderrama‐Carmona, P., Orozco‐Santa, N., Gomez, J., Gutiérrez‐Vargas, J., Moraga, R., Toledo, J., Littau, J. L., Härtel, S., et al. (2023) · Brain Pathology · doi:10.1111/bpa.13119 · Cited by 11 · see citing works
Classical-quantum interfaces in living neural tissue supporting conscious functions
(2020) · Advances in Quantum Chemistry · doi:10.1016/bs.aiq.2020.08.002 · Cited by 6 · see citing works
Chimeric brain models to study human glial-neuronal and macroglial-microglial interactions
Jin, M., Ma, Z., Zhang, H., Dang, R., Papetti, A. V., Stillitano, A. C., Zou, L., Goldman, S. A., & Jiang, P. (2026) · Cell Reports · doi:10.1016/j.celrep.2025.116794 · Cited by 6 · see citing works
Self-citation
- Authors
- Oberheim, N. A., Wang, X., Goldman, S., & Nedergaard, M.
- Affiliations
- University of Rochester Medicine (US)
- Corresponding author
- Nedergaard, Maiken
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2006-10
- Volume
- 29
- Issue
- 10
- Pages
- 547-553
- ISSN
- 0166-2236 (ISSN-L)
- OpenAlex
- W2152460583
- Cited by
- 739
- References
- 63
- Citations by year
- 2026: 22 · 2025: 41 · 2024: 38 · 2023: 39 · 2022: 48 · 2021: 53 · 2020: 48 · 2019: 37 · 2018: 32 · 2017: 42 · 2016: 48 · 2015: 42 · 2014: 47 · 2013: 40 · 2012: 42
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS38073, R01NS038073, NS 30007)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- astrocytes, protoplasmic astrocyte, astrocyte morphology, human brain evolution, cortical evolution, synaptic modulation, cortical circuits
- MeSH terms
- Adult, Animals, Astrocytes, Brain, Biological Evolution, Humans
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