BLBP-expression in astrocytes during experimental demyelination and in human multiple sclerosis lesions
Abstract
Several lines of evidence indicate that remyelination represents one of the most effective mechanisms to achieve axonal protection. For reasons that are not yet understood, this process is often incomplete or fails in multiple sclerosis (MS). Activated astrocytes appear to be able to boost or inhibit endogenous repair processes. A better understanding of remyelination in MS and possible reasons for its failure is needed. Using the well-established toxic demyelination cuprizone model, we created lesions with either robust or impaired endogenous remyelination capacity. Lesions were analyzed for mRNA expression levels by Affymetrix GeneChip® arrays. One finding was the predominance of immune and stress response factors in the group of genes which were classified as remyelination-supporting factors. We further demonstrate that lesions with impaired remyelination capacity show weak expression of the radial-glia cell marker brain lipid binding protein (BLBP, also called B-FABP or FABP7). The expression of BLBP in activated astrocytes correlates with the presence of oligodendrocyte progenitor cells. BLBP-expressing astrocytes are also detected in experimental autoimmune encephalomyelitis during the remission phase. Furthermore, highest numbers of BLBP-expressing astrocytes were evident in lesions of early MS, whereas significantly less are present at the rim of (chronic)-active lesions from patients with long disease duration. Transfection experiments show that BLBP regulates growth…
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Astrocytes show significantly lower gene and protein expression of GFAP after chronic demyelination compared to acute demyelination.
“Since astrocytes show significantly lower gene and protein expression of GFAP after chronic demyelination compared to acute demyelination”
From Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned (2014) · cites this paper as Kipp et al., 2011b
The activation status of astrocytes appears to be higher after acute demyelination than after chronic demyelination.
“the activation status of astrocytes appears to be higher after acute demyelination (Ludwin, 1980; Kipp et al., 2011b)”
From Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned (2014) · cites this paper as Kipp et al., 2011b
Under continuing cuprizone treatment, astrogliosis persists and after chronic demyelination the number of astrocytes is similar to acute demyelination.
“Under continuing cuprizone treatment astrogliosis persists and after chronic demyelination the number of astrocytes is similar to acute demyelination (Lindner et al., 2009; Kipp et al., 2011b).”
From Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned (2014) · cites this paper as Kipp et al., 2011b
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Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned
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“Due to an extensive membrane synthesis oligodendrocytes need to display a high cellular metabolism requiring a large amount of oxygen and adenosintriphosphat (ATP).”
BackgroundInfluentialSelf-citationThe Cuprizone Model: Dos and Do Nots
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“Alternatively, it might be that mature oligodendrocytes re-express proteins expressed during oligodendrocyte development, as suggested for astrocytes [38], or that OPCs are activated early during the course of cuprizone-induced demyelination.”
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Self-citation
- Authors
- Kipp, M., Gingele, S., Pott, F., Clarner, T., van der Valk, P., Denecke, B., Gan, L., Siffrin, V., Zipp, F., Dreher, W., Baumgartner, W., Pfeifenbring, S., Godbout, R., Amor, S., & Beyer, C.
- Affiliations
- RWTH Aachen University (DE)
- Johannes Gutenberg University Mainz (DE)
- University of Bremen (DE)
- Universitätsmedizin Göttingen (DE)
- University of Alberta (CA)
- Queen Mary University of London (GB)
- Corresponding author
- Kipp, M.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 25
- Issue
- 8
- Pages
- 1554-1568
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W1994743569
- Cited by
- 83
- References
- 7
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 6 · 2018: 2 · 2017: 3 · 2016: 5 · 2015: 10 · 2014: 8 · 2013: 5 · 2012: 11
- FWCI
- 6.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- GRO (submittedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- brain lipid-binding protein, FABP7, astrocytes, remyelination, multiple sclerosis, cuprizone, experimental autoimmune encephalomyelitis, oligodendrocyte precursor cells, demyelination, disease duration, gene expression, growth factor regulation, astrocyte activation
- MeSH terms
- Fatty Acid-Binding Protein 7, Adult, Aged, Animals, Astrocytes, Carrier Proteins, Cell Count, Cuprizone, Demyelinating Diseases, Encephalomyelitis, Autoimmune, Experimental, Female, Glial Fibrillary Acidic Protein, Humans, Immunohistochemistry, Male, Mice, Inbred C57BL, Middle Aged, Multiple Sclerosis, Nerve Tissue Proteins, Platelet-Derived Growth Factor, RNA, Messenger, Transfection, Blotting, Western, Fibroblast Growth Factor 2, Fluorescent Antibody Technique, Indirect, Oligonucleotide Array Sequence Analysis, Tumor Suppressor Proteins, Cell Line, Tumor, Fatty Acid-Binding Proteins, Mice, Osteopontin, Real-Time Polymerase Chain Reaction
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