Project Funding Details

Growth of cerebral gliomas and epileptogenic brain plasticity processes interact, in particular via glutamatergic signaling, which in glioblastomas promotes both the autocrine division / tumor invasion and the genesis of epileptic activities. Low-grade gliomas present in more than 80% of the cases a mutation of the enzyme IDH, resulting in a better prognosis and increased epileptogenicity. The main effect of IDH mutations is the overproduction of the oncometabolite D-2-Hydroxyglutarate (D2HG) whose structure is close to that of glutamate. Our work has shown that D2HG has dual effects: D2HG is a glutamatergic agonist at high concentrations, but has antagonist effects when associated with glutamate. The objective of this project is to deepen our knowledge of the effects of D2HG on AMPA and NMDA glutamatergic signaling, and to explore its consequences on neuronal excitability and tumor growth by 1- mapping the concentrations of D2HG and glutamate around gliomas, 2- correlating it with the presence of epileptic activities in vivo and in vitro, and 3- exploring its effects on tumor growth / infiltration in tumor tissue cultures. This research conducted exclusively on human tissue in vivo and in vitro aims at better understanding the neurobiology of glioma in order to develop antiglutamate therapeutic strategies.