Rapid disruption of axon-glial integrity in response to mild cerebral hypoperfusion
| Autor: | Barbara Zonta, Karen Horsburgh, Pawel Herzyk, Peter J. Brophy, Luke Searcy, Gillian Scullion, Jessica Smith, James McCulloch, Catherine M. Gliddon, Philip R. Holland, Anne Desmazières, Emma R. Wood, Jamie McQueen, Michell M. Reimer |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Electron Microscope Tomography Nerve Fibers Myelinated Sodium Channels Corpus Callosum Myelin Mice Myelin Basic Proteins Neurofilament Proteins Cognitive decline Axon Oligonucleotide Array Sequence Analysis Neurons Microscopy Confocal Myelin-associated glycoprotein biology General Neuroscience Age Factors Myelin-Associated Glycoprotein medicine.anatomical_structure Hypoxia-Ischemia Brain Neuroglia Signal Transduction Ankyrins Neuroscience(all) Cell Adhesion Molecules Neuronal Nerve Tissue Proteins Article White matter Ranvier's Nodes medicine Animals Nerve Growth Factors Gene Expression Profiling Myelin Basic Protein Optic Nerve Axons Myelin basic protein Mice Inbred C57BL Disease Models Animal Nerve growth factor nervous system Gene Expression Regulation NAV1.6 Voltage-Gated Sodium Channel Chronic Disease biology.protein Neuroscience Cell Adhesion Molecules |
| Zdroj: | Reimer, M M, Mcqueen, J, Searcy, L, Scullion, G, Zonta, B, Desmazieres, A, Holland, P R, Smith, J, Gliddon, C, Wood, E R, Herzyk, P, Brophy, P J, McCulloch, J & Horsburgh, K 2011, ' Rapid Disruption of Axon–Glial Integrity in Response to Mild Cerebral Hypoperfusion ', The Journal of Neuroscience, vol. 31, no. 49, pp. 18185-18194 . https://doi.org/10.1523/JNEUROSCI.4936-11.2011 |
| ISSN: | 1529-2401 |
| DOI: | 10.1523/JNEUROSCI.4936-11.2011 |
| Popis: | Myelinated axons have a distinct protein architecture which is essential for action potential propagation, neuronal communication and maintaining cognitive function. Damage to myelinated axons, associated with cerebral hypoperfusion, is suggested to contribute to age-related cognitive decline. We sought to determine whether there are selective and early alterations in the protein architecture of myelinated axons in response to cerebral hypoperfusion. Using a mouse model of hypoperfusion we assessed changes in proteins, by confocal laser scanning microscopy, critical to the maintenance of the paranodes (contactin-associated protein (CASPR); Neurofascin155 (Nfasc155)), the nodes of Ranvier (voltage-gated sodium channels (Nav1.6), Neurofascin186 (Nfasc186) and AnkyrinG), axon-glial integrity (myelin-associated glycoprotein (MAG)), axon (SMI312) and myelin (myelin basic protein (MBP)). As early as 3 days 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 confirmed by electron microscopy. Concurrent with paranodal disruption there was a significant increase in nodal length, identified by Nav1.6 staining, with hypoperfusion. In contrast, the nodal anchoring proteins AnkyrinG and Nfasc186 were unchanged and there were no changes in axonal and myelin integrity with hypoperfusion. Disruption of axon-glial integrity was also determined after hypoperfusion by changes in the spatial distribution of MAG staining. These nodal/paranodal changes were more pronounced after one month of hypoperfusion. A microarray analysis of white matter enriched samples of sham as compared with hypoperfused mice indicated that there were significant alterations in 129 genes (p |
| Databáze: | OpenAIRE |
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