| First Author | Zhao W | Year | 2015 |
| Journal | J Neurosci | Volume | 35 |
| Issue | 1 | Pages | 308-15 |
| PubMed ID | 25568123 | Mgi Jnum | J:323508 |
| Mgi Id | MGI:6880324 | Doi | 10.1523/JNEUROSCI.1944-14.2015 |
| Citation | Zhao W, et al. (2015) Extracellular glutamate exposure facilitates group I mGluR-mediated epileptogenesis in the hippocampus. J Neurosci 35(1):308-15 |
| abstractText | Stimulation of group I mGluRs elicits several forms of translation-dependent neuronal plasticity including epileptogenesis. The translation process underlying plasticity induction is controlled by repressors including the fragile X mental retardation protein (FMRP). In the absence of FMRP-mediated repression, a condition that occurs in a mouse model (Fmr1(-/-)) of fragile X syndrome, group I mGluR-activated translation is exaggerated causing enhanced seizure propensity. We now show that glutamate exposure (10 mum for 30 min) reduced FMRP levels in wild-type mouse hippocampal slices. Downregulation of FMRP was dependent on group I mGluR activation and was blocked by a proteasome inhibitor (MG-132). Following glutamate exposure, synaptic stimulation induced prolonged epileptiform discharges with properties similar to those observed in Fmr1(-/-) preparations. In both cases, prolonged epileptiform discharges were blocked by group I mGluR antagonists (LY367385 + MPEP) and their induction was prevented by protein synthesis inhibitor (anisomycin). The results suggest that stimulation of group I mGluRs during glutamate exposure caused proteolysis of FMRP. Reduction of FMRP led to enhanced synaptic group I mGluR-mediated translation. Elevated translation facilitated the recruitment of group I mGluR-mediated prolonged epileptiform discharges. |
