Aberrant neuronal differentiation is common in glioma but is associated neither with epileptic seizures nor with better survival
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Aberrant neuronal differentiation is common in glioma but is associated neither with epileptic seizures nor with better survival. / Beier, Christoph Patrick; Rasmussen, Tine; Dahlrot, Rikke Hedegaard; Tenstad, Helene Broch; Aarø, Julie Slinning; Sørensen, Mai Froberg; Heimisdóttir, Sólborg Berglind; Sørensen, Mia Dahl; Svenningsen, Per; Riemenschneider, Markus J; Beier, Dagmar; Kristensen, Bjarne Winther.
I: Scientific Reports, Bind 8, Nr. 1, 08.10.2018, s. 14965.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Aberrant neuronal differentiation is common in glioma but is associated neither with epileptic seizures nor with better survival
AU - Beier, Christoph Patrick
AU - Rasmussen, Tine
AU - Dahlrot, Rikke Hedegaard
AU - Tenstad, Helene Broch
AU - Aarø, Julie Slinning
AU - Sørensen, Mai Froberg
AU - Heimisdóttir, Sólborg Berglind
AU - Sørensen, Mia Dahl
AU - Svenningsen, Per
AU - Riemenschneider, Markus J
AU - Beier, Dagmar
AU - Kristensen, Bjarne Winther
PY - 2018/10/8
Y1 - 2018/10/8
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-018-33282-5
DO - 10.1038/s41598-018-33282-5
M3 - Journal article
C2 - 30297697
VL - 8
SP - 14965
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
ER -
ID: 364505101