|
| Status |
Public on Aug 05, 2008 |
| Title |
Alterations in Neuronal Gene Expression Profiles in Response to Experimental Demyelination and Axonal Transection |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
|
| Summary |
The pathological basis of multiple sclerosis involves damage to both myelin sheaths and axons. Demyelination and axonal transection are considered to cause reversible and irreversible neurological deficits respectively, gradually destroying the neuronal circuitry of the CNS. In order to analyse the individual effects of the pathological hallmarks of multiple sclerosis on neurons, the pontocerebellar pathway was targeted with either lysolecithin-induced chemical demyelination or complete pathway transection. Transcriptional changes in the pontocerebellar neuronal nuclei were investigated with microarrays at days 4, 10 and 37 post-intervention to identify underlying molecular responses. A common as well as unique set of injury response genes was identified in the transection and the demyelination conditions. The increased expression of activating transcription factor 3 (Atf3) and thyrotropin-releasing hormone (Trh) in both injury paradigms was validated by immunohistochemistry. Expression of Atf3 in a patient with Marburg’s variant of multiple sclerosis was also detected in the pons with large cerebellar demyelination, confirming the activation of the Atf3 pathway in a human disease sample as well. This experimental approach may be useful for the identification of pathways that could be targeted for remyelinative and neuroprotective drug development.
|
| |
|
| Overall design |
The pontine nuclei containing the neuronal cell bodies of the projecting lesioned axons (saline, lysolecithin or transection) were collected at different time points post-intervention (day 4, day 10, and day 37), and assayed for changes in gene expression caused by the distal injury site. The contralateral pontine nuclei were used as controls.
CEL files lost
|
| |
|
| Contributor(s) |
Lovas G, Nielsen JA, Johnson KR, Hudson lD |
| Citation(s) |
20086029 |
| Submission date |
Aug 03, 2008 |
| Last update date |
Feb 21, 2017 |
| Contact name |
Joe A Nielsen |
| E-mail(s) |
nielsenj@ninds.nih.gov
|
| Phone |
301-402-7350
|
| Organization name |
NIH/NINDS
|
| Lab |
Section of Develpmental Genetics
|
| Street address |
49 Convent Drive BD49,5A75
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892-4479 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL85 |
[RG_U34A] Affymetrix Rat Genome U34 Array |
|
| Samples (16)
|
|
| Relations |
| BioProject |
PRJNA113555 |
Less...
More...