Beier, Christoph Patrick and Rasmussen, Tine and Dahlrot, Rikke Hedegaard and Tenstad, Helene Broch and Aaro, Julie Slinning and Sorensen, Mai Froberg and Heimisdottir, Solborg Berglind and Sorensen, Mia Dahl and Svenningsen, Per and Riemenschneider, Markus J. and Beier, Dagmar and Kristensen, Bjarne Winther (2018) Aberrant neuronal differentiation is common in glioma but is associated neither with epileptic seizures nor with better survival. SCIENTIFIC REPORTS, 8: 14965. ISSN 2045-2322,
Full text not available from this repository. (Request a copy)Abstract
The mechanisms of glioma-associated seizures (GAS) have yet to be fully elucidated. Proneural subtype, isocitrate dehydrogenase 1 (IDH1) mutations, and epileptic seizures are closely associated suggesting that aberrant neuronal differentiation contributes to glioma-associated seizures. In a population-based cohort (n = 236), lack of stem cell marker expression (nestin, musashi) was significantly associated with IDH1 mutations and GAS at diagnosis. In vitro data suggested an association of IDH1 mutations and a more differentiated phenotype. Out of eight glioma stem cell (GSC) lines, seven revealed positivity for the synaptic marker protein synaptophysin. Three had synapse-like structures identified by electron microscopy and were either vGlut1 (glutamatergic) or GAD67 (GABAergic) positive. In vivo, >10% synaptophysin-positive tumour cells were present in >90% of all gliomas. Synaptophysin expression was associated with proneural subtype and vGlut1 expression, suggesting that most synapse-like structures in glioma are glutamatergic. However, we found null associations between vGlut1 protein/mRNA expression and survival, GAS at onset, development of GAS after resection, and refractory GAS. Synapse-like structures were neither functional nor activated by spontaneous action potentials or cellular networks. Thus, aberrant neuronal differentiation including glutamatergic synapse-like structures is detectable in glioma but is associated neither with epileptic seizures nor with better survival.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CANCER STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; HIGH-GRADE GLIOMAS; BRAIN-TUMORS; PREDICT PROGNOSIS; GLUTAMATE RELEASE; GLIOBLASTOMA; EXPRESSION; TEMOZOLOMIDE; IDH1; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Neuropathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Dec 2019 13:14 |
| Last Modified: | 05 Dec 2019 13:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13704 |
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