Activation of Inflammatory Response by a Combination of Growth Factors in Cuprizone-Induced Demyelinated Brain Leads to Myelin Repair
Abstract
In vivo remyelination promoted by a combination of four oligodendrocyte specific growth factors (GFs) in cuprizone-induced demyelinated mice brains was described recently by our group. Here we report activation of inflammatory response in mice brain following cuprizone-induced demyelination and its further enhancement immediately after injection of growth factors in vivo, while no significant inflammatory response was evident in GFs-injected normal brains. Cuprizone-induced demyelination was accompanied by increased expression of inflammatory cytokines, TNFalpha and IL-1beta, anti-inflammatory cytokines TGFbeta, IL-10 and increased levels of chemokines, CCL2, CCL5, and CXCL10, produced by resident microglia and astrocytes. During demyelination, involvement of oxidative stress was evident by disruption of mitochondrial structure and temporal decline in reduced glutathione levels, later returning to normal. Increase in the cytokines and chemokines was further enhanced within 2 days post injection (dpi) of GFs, coinciding with signal for repair via activation of pAkt and NFkappaB transcription factor reported earlier. Upregulation of mRNA and protein level of antioxidant genes, metallothionein (MT) I/II and activity of a cytosolic oxidoreductase enzyme, glycerolphosphate-3 dehydrogenase (cGPDH) occurred, resulting in a metabolic shuttle with an increase in glycerol in mice brains during period of demyelination and early GF-mediated repair.
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Cuprizone selectively affects oligodendrocytes.
“Nevertheless, a consensus seems to be that cuprizone selectively affects oligodendrocytes.”
From Strain differences in cuprizone induced demyelination (2017) · cites this paper as [22]
Cites
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“Furthermore, oligodendrocytes possess only a little amount of the anti-oxidative enzyme, glutathione, which also declines upon cuprizone treatment, but in comparison to other brain cells the highest amount of iron (Thorburne and Juurlink, 1996; Biancotti et al., 2008).”
BackgroundCXCL10 Triggers Early Microglial Activation in the Cuprizone Model
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- Authors
- Biancotti, J. C., Kumar, S., & de Vellis, J.
- Affiliations
- University of California, Los Angeles (US)
- Venue
- Neurochemical Research
- Published
- 2008-07-26
- Volume
- 33
- Issue
- 12
- Pages
- 2615-2628
- ISSN
- 0364-3190 (ISSN-L)
- 1573-6903
- OpenAlex
- W2023306486
- Cited by
- 69
- References
- 6
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 6 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 4 · 2016: 6 · 2015: 4 · 2014: 6 · 2013: 2 · 2012: 3
- FWCI
- 3.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neurochemical Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-06576, P01HD006576)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- cuprizone-induced demyelination, remyelination, inflammation, microglia, astrocytes, cytokines, chemokines, oxidative stress, mitochondrial damage, glutathione, metallothionein, glycerol, pAKT, NF-κB, demyelinating disease
- MeSH terms
- Animals, Base Sequence, Brain Diseases, Cuprizone, Demyelinating Diseases, Female, Growth Substances, Immunohistochemistry, Inflammation, Mice, Inbred C57BL, Microscopy, Electron, Myelin Sheath, Magnetic Resonance Spectroscopy, Cytokines, DNA Primers, Inflammation Mediators, Reverse Transcriptase Polymerase Chain Reaction, Mice
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