Loss of astrocytic domain organization in the epileptic brain
Open accessAbstract
Gliosis is a pathological hallmark of posttraumatic epileptic foci, but little is known about these reactive astrocytes beyond their high glial fibrillary acidic protein (GFAP) expression. Using diolistic labeling, we show that cortical astrocytes lost their nonoverlapping domain organization in three mouse models of epilepsy: posttraumatic injury, genetic susceptibility, and systemic kainate exposure. Neighboring astrocytes in epileptic mice showed a 10-fold increase in overlap of processes. Concurrently, spine density was increased on dendrites of excitatory neurons. Suppression of seizures by the common antiepileptic, valproate, reduced the overlap of astrocytic processes. Astrocytic domain organization was also preserved in APP transgenic mice expressing a mutant variant of human amyloid precursor protein despite a marked upregulation of GFAP. Our data suggest that loss of astrocytic domains was not universally associated with gliosis, but restricted to seizure pathologies. Reorganization of astrocytes may, in concert with dendritic sprouting and new synapse formation, form the structural basis for recurrent excitation in the epileptic brain.
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Each astrocyte is in contact with up to four capillaries and enwraps about four neuronal cell bodies and 105 synapses.
“Interposed between neurons and the vasculature, each astrocyte is in contact with up to four capillaries and enwraps about four neuronal cell bodies and 105 synapses [395,396,397].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [396]
The Introduction (page unavailable) estimates that one astrocytic domain encompasses about 140,000 synapses in rodents, broadly supporting the claim’s 10^5-synapse figure; it gives a different estimate of 2,000,000 for humans. The passages found do not support the specific counts of up to four capillaries or about four neuronal cell bodies per astrocyte. (LLM, conf=0.86)
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Cites
Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons
Nagai, M., Re, D. B., Nagata, T., Chalazonitis, A., Jessell, T. M., Wichterle, H., & Przedborski, S. (2007) · Nature Neuroscience · doi:10.1038/nn1876 · Cited by 1,220 · see citing works
A population-based study of seizures after traumatic brain injuries
Annegers, J. F., Hauser, W. A., Coan, S. P., & Rocca, W. A. (1998) · New England Journal of Medicine · doi:10.1056/nejm199801013380104 · Cited by 1,090 · see citing works
Wilhelmsson, U., Bushong, E. A., Price, D. L., Smarr, B. L., Phung, V., Terada, M., Ellisman, M. H., & Pekny, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602841103 · Cited by 643 · cited 3× · see citing works
“This difference may also explain why a recent report con- cluded that the size of astrocytic domains did not increase during reactive gliosis (Wilhelmsson et al., 2006).”
BackgroundInfluentialRegulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2
Tavazoie, S. F., Alvarez, V. A., Ridenour, D. A., Kwiatkowski, D. J., & Sabatini, B. L. (2005) · Nature Neuroscience · doi:10.1038/nn1566 · Cited by 497 · see citing works
Seizures and myoclonus in patients with Alzheimer's disease
Hauser, W. A., Morris, M. L., Heston, L. L., & Anderson, V. E. (1986) · Neurology · doi:10.1212/wnl.36.9.1226 · Cited by 336 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Frey LC (2003) Epidemiology of posttraumatic epilepsy: a critical review. Epilepsia 44 [Suppl 10]:11-17.
- Loscher W (2002) Basic pharmacology of valproate: a review after 35 years of clinical use for the treatment of epilepsy. CNS Drugs 16:669 -694.
- McGraw J, Hiebert GW, Steeves JD (2001) Modulating astrogliosis after neurotrauma. J Neurosci Res 63:109 -115.
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Xie, L., Kang, H., Xu, Q., Chen, M. J., Liao, Y., Thiyagarajan, M., O’Donnell, J., Christensen, D. J., Nicholson, C., Iliff, J. J., et al. (2013) · Science · doi:10.1126/science.1241224 · Cited by 5,411 · see citing works
Self-citationAstrocytes: Biology and pathology
Sofroniew, M. V., & Vinters, H. V. (2010) · Acta Neuropathologica · doi:10.1007/s00401-009-0619-8 · Cited by 5,196 · see citing works
Astrocyte reactivity and reactive astrogliosis: costs and benefits
Pekny, M., & Pekna, M. (2014) · Physiological Reviews · doi:10.1152/physrev.00041.2013 · Cited by 934 · see citing works
Wanner, I. B., Anderson, M. A., Song, B., Levine, J., Fernandez, A., Gray-Thompson, Z., Ao, Y., & Sofroniew, M. V. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2121-13.2013 · Cited by 839 · see citing works
Elusive roles for reactive astrocytes in neurodegenerative diseases
Ben Haim, L., Carrillo-de Sauvage, M.-A., Ceyzériat, K., & Escartin, C. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00278 · Cited by 453 · see citing works
Budde, M. D., Janes, L., Gold, E., Turtzo, L. C., & Frank, J. A. (2011) · Brain · doi:10.1093/brain/awr161 · Cited by 408 · see citing works
Emerging role for astroglial networks in information processing: from synapse to behavior
Pannasch, U., & Rouach, N. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.04.004 · Cited by 251 · see citing works
Astrocyte Endfeet in Brain Function and Pathology: Open Questions
Díaz-Castro, B., Robel, S., & Mishra, A. (2023) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-091922-031205 · Cited by 238 · see citing works
Neuronal Transgene Expression in Dominant-Negative SNARE Mice
Fujita, T., Chen, M. J., Li, B., Smith, N. A., Peng, W., Sun, W., Toner, M. J., Kress, B. T., Wang, L., Benraiss, A., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.2585-14.2014 · Cited by 141 · see citing works
Self-citationAstroglia In Neurological Diseases
Verkhratsky, A., Rodríguez, J. J., & Parpura, V. (2013) · Future Neurology · doi:10.2217/fnl.12.90 · Cited by 140 · see citing works
Garcia, O., Torres, M., Helguera, P., Coskun, P., & Busciglio, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0014200 · Cited by 122 · see citing works
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Bedner, P., Jabs, R., & Steinhäuser, C. (2020) · Glia · doi:10.1002/glia.23725 · Cited by 71 · see citing works
Herzer, S., Hagan, C., von Gerichten, J., Dieterle, V., Munteanu, B., Sandhoff, R., Hopf, C., & Nordström, V. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00206 · Cited by 27 · see citing works
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- Authors
- Oberheim, N. A., Tian, G.-F., Han, X., Peng, W., Takano, T., Ransom, B., & Nedergaard, M.
- Affiliations
- University of Rochester Medicine (US)
- University of Washington (US)
- Corresponding author
- Nedergaard, Maiken
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-03-26
- Volume
- 28
- Issue
- 13
- Pages
- 3264-3276
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6670598
- OpenAlex
- W2094240884
- Cited by
- 303
- References
- 5
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 10 · 2023: 14 · 2022: 21 · 2021: 15 · 2020: 13 · 2019: 19 · 2018: 15 · 2017: 22 · 2016: 20 · 2015: 13 · 2014: 22 · 2013: 29 · 2012: 21
- FWCI
- 12.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (T32GM07356, T32GM007356)
- National Institute of Neurological Disorders and Stroke (R01NS030007, R01NS038073, NS038073, NS030007, NS50315, P01NS050315)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- astrocytes, gliosis, epilepsy, post-traumatic epilepsy, kainate-induced epilepsy, genetic epilepsy model, glial fibrillary acidic protein, dendritic spine density, valproic acid, amyloid precursor protein, APP transgenic mice, recurrent excitation
- MeSH terms
- Amino Acids, Animals, Anticonvulsants, Astrocytes, Behavior, Animal, Brain, Dendrites, Disease Models, Animal, Electroencephalography, Epilepsy, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Kainic Acid, Luminescent Proteins, Mice, Transgenic, Nerve Tissue Proteins, Neurons, Time Factors, Valproic Acid, Amyloid beta-Protein Precursor, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins
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