Table 3.
Roles of Group II mGluRs in epileptogenesis
| Receptor | Mechanism | Signaling pathway | Model organism | Epilepsy inducer | Reference |
|---|---|---|---|---|---|
| mGluR2 | Astrogliosis, cellular hypertrophy, water homeostasis, inflammation, modulation of excitatory neurotransmission | GluR2 receptor and KA receptor ↓→Ca2+↑ | TLE patients | Das et al., 2012 | |
| mGluR2/3 | Excitatory synaptic transmission | Group II mGluRs↑→release of glutamate onto pyramidal neurons ↓→epileptogenesis | Pyramidal neurons of cortical layers 2–3 in acute slices derived from surgically removed cortical tissue of people with epilepsy | Bocchio et al., 2018 | |
| mGluR2/3 | Disruption of glutamate-mediated homeostasis of neuronal excitability | Drosophila GluRA mutations→PI3K activation↓, FOXO↑→neuronal excitability | Drosophila (UAS-PI3K DN and UAS-PI3K-CAAX transgenes) | Electrical stimulation (10 Hz) | Howlett et al., 2008; Lovisari et al., 2021 |
| mGluR2/3 | Involvement in the generation and propagation of epilepsy in the entorhinal cortex | LY354740→K+ conductance↑→Na+-permeable channel↓→neuronal excitability and epileptiform activity↓ | Sprague-Dawley rats | PTX (100 mM) | Zhang et al., 2015 |
| mGluR3 | Seizure-induced upregulation of mGluR3 | Mesial temporal lobe epilepsy→mGluR3↑→TGF-β↑ | Male Sprague-Dawley rats | Intermittent electrical stimulation (10-s trains of 50 Hz biphasic square pulses); max. stimulus intensity: 500 μA) | Aronica et al., 2000; Kovalenko et al., 2022; Celli et al., 2023 |
| mGluR2 | Synergistic interactions with the antiseizure drug levetiracetam and the positive allosteric modulator JNJ-46356479 | Adult male CF-1 mice | Electrical stimulation (6 Hz, 32 or 44 mA) | Metcalf et al., 2018 |
FoxO: Forkhead box O; LY354740: hexane-2,6-dicarboxylic acid; mGluR: metabotropic glutamate receptor; PI3K: phosphoinositide 3-kinase; PTX: Picro-toxin; TLE: temporal lobe epilepsy.