Anticonvulsive effect of a selective mGluR8 agonist (S)-3,4-dicarboxyphenylglycine (S-3,4-DCPG) in the mouse pilocarpine model of status epilepticus.
OBJECTIVE
We sought to investigate the anticonvulsive and neuroprotective effect of a selective metabotropic glutamate receptor 8 (mGluR8) agonist (S)-3,4-dicarboxyphenylglycines (S-3,4-DCPG) on pilocarpine-induced status epilepticus (PISE) and subsequent loss of hilar neurons in the dentate gyrus after systemic (intravenous) or local (intracerebroventricular) administration. We compared the difference in granular cell responses after paired-pulse stimulation of the perforant pathway and the sensitivity to local injection of S-3,4-DCPG into the stratum granulosum in the control and mice at 2 months after PISE.


METHODS
We used intravenous, intracerebroventricular, or intrahippocampal administration of S-3,4-DCPG to mice with status epilepticus or temporal lobe epilepsy and neurophysiologic recording of somatic field excitatory postsynaptic potential (sfEPSP) and population spike (PS) of granular cells in response to perforant-pathway stimulation or S-3,4-DCPG treatment.


RESULTS
Intracerebroventricular (1.91 micromol) but not systemic administration of S-3,4-DCPG (at doses of 12.5, 50, 100, 200, 400, 800, and 1,200 mg/kg) could control PISE with no neuroprotective effect. In epileptic mice, mGluR8-mediated inhibition of fEPSPs was reduced significantly in granular cell bodies.


CONCLUSIONS
At doses ranging from 12.5 to 1,200 mg/kg, intravenous administration of S-3,4-DCPG may not be effective in controlling status epilepticus. Down-regulation of mGluR8 may be related to reduced S-3,4-DCPG-mediated inhibition and the subsequent occurrence of spontaneously recurrent seizures.
Jiang
Feng Li
FL
Epilepsy Research Lab, National Neuroscience Institute, Singapore.
Tang
Yong Cheng
YC
Chia
Shwn Chin
SC
Jay
Therese M
TM
Tang
Feng Ru
FR
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004833:Epilepsy, Temporal Lobe / Q000473:pathology / Q000517:prevention & control; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D051379:Mice; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D019580:Perforant Pathway / Q000187:drug effects / Q000502:physiology; D010862:Pilocarpine; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013226:Status Epilepticus / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*
C110733:3,4-dicarboxyphenylglycine; D000927:Anticonvulsants; D001565:Benzoates; D018094:Receptors, Metabotropic Glutamate; C111435:metabotropic glutamate receptor 8; D010862:Pilocarpine; D005998:Glycine