| Autor: |
Nadine Jaenisch, Anke Popp, Madlen Guenther, Juliane Schnabel, Otto W. Witte, Christiane Frahm |
| Jazyk: |
angličtina |
| Rok vydání: |
2014 |
| Předmět: |
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| Zdroj: |
Neurobiology of Disease, Vol 70, Iss , Pp 237-244 (2014) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1016/j.nbd.2014.06.015 |
| Popis: |
Following cerebral injuries such as stroke, a structural and functional reorganization of the impaired tissue occurs, which is often accompanied by a re-expression of developmental genes. During brain development, embryonic splice variants of the GABA-synthesizing GAD67 gene (collectively termed EGAD) participate in cell proliferation, migration, and neuronal differentiation. We thus hypothesized an involvement of EGAD in post-ischemic plasticity. EGAD transcripts were up-regulated at early reperfusion times in the injured area following transient middle cerebral artery occlusion (with a peak expression of 4.5-fold at 6 h in C57BL/6 mice). Cell-specific analysis by a combination of radioactive in situ hybridization and immunolabeling revealed EGAD up-regulation in TUNEL-positive neurons. This unexpected cell death-associated expression of EGAD was confirmed in cell culture models of ischemia (combined oxygen–glucose deprivation) and apoptosis (staurosporine). Staurosporine-mediated cell death led to cleaved Caspase-3 activation, a key regulator of apoptosis following stroke. Blocking of staurosporine-associated EGAD expression via antisense RNA treatment reduced cleaved Caspase-3 activation by ~30%. In addition to the involvement of EGAD in proliferative processes during brain development, we found here that EGAD participates in cell death under pathophysiological conditions in the adult brain. Re-expression of EGAD in neurons following stroke may play a role in aberrant cell cycle activation, consequently being pro-apoptotic. Our observation of a new GABA related pro-apoptotic mechanism and its successful modification might be of significant clinical relevance. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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