| Title: |
Rapid Disruption of Axon-Glial Integrity in Response to Mild Cerebral Hypoperfusion. |
| Authors: |
Reimer, Michell M.; McQueen, Jamie; Searcy, Luke; Scullion, Gillian; Zonta, Barbara; Desmazieres, Anne; Holland, Philip R.; Smith, Jessica; Gliddon, Catherine; Wood, Emma R.; Herzyk, Pawel; Brophy, Peter J.; McCulloch, James; Horsburgh, Karen |
| Source: |
Journal of Neuroscience; 12/7/2011, Vol. 31 Issue 49, p18185-18194, 10p |
| Subject Terms: |
Axons; Action potentials; Cognitive ability; Proteins in the body; Laboratory mice; Cellular signal transduction; Cytokines |
| Abstract: |
Myelinated axons have a distinct protein architecture essential for action potential propagation, neuronal communication, and maintaining cognitive function. Damage to myelinated axons, associated with cerebral hypoperfusion, contributes to age-related cognitive decline. We sought to determine early alterations in the protein architecture of myelinated axons and potential mechanisms after hypoperfusion. Using a mouse model of hypoperfusion, we assessed changes in proteins critical to the maintenance of paranodes, nodes of Ranvier, axon- glial integrity, axons, and myelin by confocal laser scanning microscopy. As early as 3 d after hypoperfusion, the paranodal septate-like junctions were damaged. This was marked by a progressive reduction of paranodal Neurofascin signal and a loss of septate-like junctions. Concurrent with paranodal disruption, there was a significant increase in nodal length, identified by Nav1.6 staining, with hypoperfusion. Disruption of axon- glial integrity was also determined after hypoperfusion by changes in the spatial distribution of myelin-associated glycoprotein staining. These nodal/paranodal changes were more pronounced after 1 month of hypoperfusion. In contrast, the nodal anchoring proteins AnkyrinG and Neurofascin 186 were unchanged and there were no overt changes in axonal and myelin integrity with hypoperfusion. A microarray analysis of white matter samples indicated that there were significant alterations in 129 genes. Subsequent analysis indicated alterations in biological pathways, including inflammatory responses, cytokinecytokine receptor interactions, blood vessel development, and cell proliferation processes. Our results demonstrate that hypoperfusion leads to a rapid disruption of key proteins critical to the stability of the axon- glial connection that is mediated by a diversity of molecular events. [ABSTRACT FROM AUTHOR] |
| : |
Copyright of Journal of Neuroscience is the property of Society for Neuroscience and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |