Gangliogliomas (GGs), composed of dysmorphic neurons and neoplastic astroglia, represent the most frequent
tumor entity associated with chronic recurrent epileptic
seizures. So far, a systematic analysis of potential differences in neurochemical profiles of dysmorphic tumoral neurons as well as neurons of the peritumoral microenvironment (PTME) was hampered by the inability to unequivocally differentiate between the distinct neuronal components in human GG biopsies. Here, we have applied a novel GG mouse model that allows to clearly resolve the neurochemical profiles of GG-intrinsic versus PTME neurons. For this purpose, glioneuronal
tumors in mice were induced by intraventricular in utero electroporation (IUE) of piggyBac-based plasmids for BRAFV600E and activated Akt (AktT308D/S473D, further referred to as AktDD) and analyzed neurochemically by immunocytochemistry against specific marker
proteins. IUE of BRAFV600E/AktDD in mice resulted in
tumors with the morphological features of human GGs. Our immunocytochemical analysis revealed a strong reduction of GABAARα1 immunoreactivity in the
tumor compared to the PTME. In contrast, the extent of
NMDAR1 immunoreactivity in the
tumor appeared comparable to the PTME. Interestingly,
tumor cells maintained the potential to express both receptors. Fittingly, the abundance of the presynaptic
vesicular neurotransmitter transporters VGLUT1 and VGAT was also decreased in the
tumor. Additionally, the fraction of
parvalbumin and
somatostatin nonneoplastic interneurons was reduced. In conclusion, changes in the levels of key
proteins in
neurotransmitter signaling suggest a loss of synapses and may thereby lead to neuronal network alterations in mouse GGs.