Table 4.
Roles of Group III mGluRs in epileptogenesis
| Receptor | Mechanism | Signaling pathway | Model organism | Epilepsy inducer | Reference |
|---|---|---|---|---|---|
| mGluR7 | Antagonism of mGluR7 | GIPC1↓→mGluR7↓→more and longer abnormal brain discharges in LFP | TLE patients and adult male C57BL/6 mice | KA (50 nL of a 20 mM solution) | Liu et al., 2022a |
| mGluR4 | mGluR4 knock-down | mGluR4↓→excitatory activity and seizure-associated vulnerability of hippocampal neurons↑→ severe seizure activity↑ | mGluR4-KO mice | Kumar et al., 2022 | |
| mGluR4, mGluR6, mGluR8 | Divergent patterns of associational-commissural-CA3 and SC-CA1 synapse depression in SE | mGluR4, mGluR6↓, mGluR8↑→synaptic depression→chronic epilepsy | Male Wistar rats | Pilocarpine hydrochloride (340 mg/kg) | Dammann et al., 2018 |
| Group III mGluRs | Excitotoxic action of 4-aminopyridine | Extracellular glutamate↑→mGluR III↑→seizure↓ | Male Wistar rats | 4-aminopyridine (7 mM) | Vera and Tapia, 2012 |
| Group III mGluRs | Neurotransmitter shift towards increased production of excitatory amino acids | mGluR III↓→GABA, alanine, taurine, and glutamine/GABA ratio↑→seizure | Adult male Wistar rats | PTZ (35 mg/kg) | Zhai et al., 2021; Zhao et al., 2022 |
| mGluR7 | Interaction between mGluR7 and PDZ proteins | Targeted mutation of the mGluR7a C terminus →disrupted interaction with PDZ proteins →EEG discharges | Adult Sprague-Dawley rats | Liu et al., 2022b; Tuduri et al., 2022 | |
| Group III mGluRs | Selective downregulation of group III mGluRs and dysregulated glutamatergic synaptic transmission | Elfn2 knockout→ selective downregulation of group III mGluRs and dysregulated glutamatergic synaptic transmission→seizure susceptibility↑ | HEK 293T/17 cells | Dunn et al., 2019 | |
| Group III mGluRs | Decreased expression of group III genes in the hippocampus and temporal cortex | Group III genes↓→mGluRs III expression ↓→epileptogenesis | Male Wistar rats | Pilocarpine (20–40 mg/kg) | Kovalenko et al., 2022 |
| mGluR7 | Interactions between extracellular leucine-rich repeat fibronectin domain-containing family proteins (Elfn1 and Elfn2) and mGluRs | Activation of mGluR7 by Elfn1→glutamate levels↓ | Elfn1/2-KO mice | Matsunaga and Aruga, 2021 |
EEG: Electroencephalography; GABA: gamma aminobutyric acid; KA: kainic acid; KO: knockout; LFP: local field potential; mGluRs: metabotropic glutamate receptors; TLE: temporal lobe epilepsy.