| Title |
Protective potential of dimethyl fumarate in a mouse model of thalamocortical demyelination
|
|---|---|
| Published in |
Brain Structure and Function, May 2018
|
| DOI | 10.1007/s00429-018-1680-7 |
| Pubmed ID | |
| Authors |
Manuela Cerina, Venu Narayanan, Anna Delank, Patrick Meuth, Stephanie Graebenitz, Kerstin Göbel, Alexander M. Herrmann, Stefanie Albrecht, Thiemo Daldrup, Thomas Seidenbecher, Ali Gorji, Tanja Kuhlmann, Heinz Wiendl, Christoph Kleinschnitz, Erwin J. Speckmann, Hans-Christian Pape, Sven G. Meuth, Thomas Budde |
| Abstract |
Alterations in cortical cellular organization, network functionality, as well as cognitive and locomotor deficits were recently suggested to be pathological hallmarks in multiple sclerosis and corresponding animal models as they might occur following demyelination. To investigate functional changes following demyelination in a well-defined, topographically organized neuronal network, in vitro and in vivo, we focused on the primary auditory cortex (A1) of mice in the cuprizone model of general de- and remyelination. Following myelin loss in this model system, the spatiotemporal propagation of incoming stimuli in A1 was altered and the hierarchical activation of supra- and infragranular cortical layers was lost suggesting a profound effect exerted on neuronal network level. In addition, the response latency in field potential recordings and voltage-sensitive dye imaging was increased following demyelination. These alterations were accompanied by a loss of auditory discrimination abilities in freely behaving animals, a reduction of the nuclear factor-erythroid 2-related factor-2 (Nrf-2) protein in the nucleus in histological staining and persisted during remyelination. To find new strategies to restore demyelination-induced network alteration in addition to the ongoing remyelination, we tested the cytoprotective potential of dimethyl fumarate (DMF). Therapeutic treatment with DMF during remyelination significantly modified spatiotemporal stimulus propagation in the cortex, reduced the cognitive impairment, and prevented the demyelination-induced decrease in nuclear Nrf-2. These results indicate the involvement of anti-oxidative mechanisms in regulating spatiotemporal cortical response pattern following changes in myelination and point to DMF as therapeutic compound for intervention. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 58 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 58 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 12 | 21% |
| Student > Ph. D. Student | 8 | 14% |
| Student > Master | 5 | 9% |
| Student > Bachelor | 4 | 7% |
| Student > Doctoral Student | 3 | 5% |
| Other | 10 | 17% |
| Unknown | 16 | 28% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 16 | 28% |
| Medicine and Dentistry | 7 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 9% |
| Agricultural and Biological Sciences | 4 | 7% |
| Biochemistry, Genetics and Molecular Biology | 2 | 3% |
| Other | 6 | 10% |
| Unknown | 18 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 May 2018.
All research outputs
#21,697,638
of 24,217,893 outputs
Outputs from Brain Structure and Function
#1,524
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Outputs of similar age
#291,790
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Outputs of similar age from Brain Structure and Function
#27
of 31 outputs
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