The mGlu7 receptor provides protective effects against epileptogenesis and epileptic seizures

被引：17

作者：

Girard, Benoit ^{[1
]}

Tuduri, Pola ^{[1
]}

Moreno, Maria Paula ^{[1
]}

Sakkaki, Sophie ^{[1
]}

Barboux, Cedric ^{[2
]}

Bouschet, Tristan ^{[1
]}

Varrault, Annie ^{[1
]}

Vitre, Jihane ^{[1
]}

McCort-Tranchepain, Isabelle ^{[2
]}

Dairou, Julien ^{[2
]}

Acher, Francine ^{[2
]}

Fagni, Laurent ^{[1
]}

Marchi, Nicola ^{[1
]}

Perroy, Julie ^{[1
]}

Bertaso, Federica ^{[1
]}

机构：

[1] Univ Montpellier, INSERM, CNRS, IGF, Montpellier, France

[2] Univ Paris 05, CNRS, UMR8601, Paris, France

来源：

NEUROBIOLOGY OF DISEASE | 2019年 / 129卷

关键词：

Epilepsy; Neuropharmacology; Metabotropic glutamate receptor; Animal models; Seizures; METABOTROPIC GLUTAMATE RECEPTORS; TEMPORAL-LOBE EPILEPSY; KAINATE MOUSE MODEL; MICE LACKING; ALLOSTERIC MODULATION; ANTIEPILEPTIC DRUGS; ACTIVATION; ABSENCE; STRESS; RAT;

D O I：

10.1016/j.nbd.2019.04.016

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Finding new targets to control or reduce seizure activity is essential to improve the management of epileptic patients. We hypothesized that activation of the pre-synaptic and inhibitory metabotropic glutamate receptor type 7 (mGlu7) reduces spontaneous seizures. We tested LSP2-9166, a recently developed mGlu7/4 agonist with unprecedented potency on mGlu7 receptors, in two paradigms of epileptogenesis. In a model of chemically induced epileptogenesis (pentylenetetrazole systemic injection), LSP2-9166 induces an anti-epileptogenic effect rarely observed in preclinical studies. In particular, we found a bidirectional modulation of seizure progression by mGlu4 and mGlu7 receptors, the latter preventing kindling. In the infra-hippocampal injection of kainic acid mouse model that mimics the human mesial temporal lobe epilepsy, we found that LSP2-9166 reduces seizure frequency and hippocampal sclerosis. LSP2-9166 also acts as an anti-seizure drug on established seizures in both models tested. Specific modulation of the mGlu7 receptor could represent a novel approach to reduce pathological network remodeling.

引用

页码：13 / 28

页数：16

共 61 条

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