GFAP Is Necessary for the Integrity of CNS White Matter Architecture and Long-Term Maintenance of Myelination
Open accessAbstract
To investigate the structural role of glial fibrillary acidic protein (GFAP) in vivo, mice carrying a null mutation in GFAP were generated. In 7/14 mutant animals older than 18 months of age, hydrocephalus associated with white matter loss was detected. Mutant mice displayed abnormal myelination including the presence of actively myelinating oligodendrocytes in adults, nonmyelinated axons in optic nerve, and reduced myelin thickness in spinal cord. White matter was poorly vascularized and the blood-brain barrier was structurally and functionally impaired. Astrocytic structure and function were abnormal, consisting of shortened astrocytic cell processes, decreased septation of white matter, and increased CNS extracellular space. Thus, GFAP expression is essential for normal white matter architecture and blood-brain barrier integrity, and its absence leads to late-onset CNS dysmyelination.
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Astrocytes, microglia, and endothelial cells establish tightly articulated physical and molecular interactions in a functionally integrated structure known as the gliovascular unit (GVU), through which many properties of the brain are maintained.
“Astrocytes, microglia, and endothelial cells establish tightly articulated physical and molecular interactions [1, 2, 3, 4] in a functionally integrated structure known as the gliovascular unit (GVU) [5] through which many of the properties of the brain are maintained [3, 4].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [4]
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- Authors
- Liedtke, W., Edelmann, W., Bieri, P. L., Chiu, F., Cowan, N. J., Kucherlapati, R., & Raine, C. S.
- Affiliations
- Albert Einstein College of Medicine (US)
- New York University (US)
- Corresponding author
- Wolfgang Liedtke
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1996-10
- Volume
- 17
- Issue
- 4
- Pages
- 607-615
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2012893265
- Cited by
- 538
- References
- 2
- Citations by year
- 2026: 9 · 2025: 21 · 2024: 21 · 2023: 14 · 2022: 16 · 2021: 26 · 2020: 17 · 2019: 17 · 2018: 14 · 2017: 21 · 2016: 20 · 2015: 20 · 2014: 12 · 2013: 21 · 2012: 15
- FWCI
- 5.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuron (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS-08952, T32NS007098, NS-11920, R01NS008952, NS 07098)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- glial fibrillary acidic protein, white matter integrity, myelination, dysmyelination, oligodendrocytes, blood-brain barrier, astrocytes, hydrocephalus, optic nerve, extracellular space, central nervous system development
- MeSH terms
- Aging, Animals, Blastocyst, Brain, Chimera, Corpus Callosum, Crosses, Genetic, Female, Glial Fibrillary Acidic Protein, Genetic Carrier Screening, Male, Membrane Glycoproteins, Mice, Inbred C57BL, Optic Nerve, Spinal Cord, Stem Cells, Microscopy, Immunoelectron, Mice, Knockout, Caenorhabditis elegans Proteins, Mice, Receptors, Notch
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