Group I metabotropic glutamate receptor-mediated long-term depression is disrupted in the hippocampus of WAG/Rij rats modelling absence epilepsy

Di Cicco, Gabriele, Marzano, Emanuela, Iacovelli, Luisa , Celli, Roberta, van Luijtelaar, Gilles, Nicoletti, Ferdinando, Ngomba, Richard and Wall, Mark (2021) Group I metabotropic glutamate receptor-mediated long-term depression is disrupted in the hippocampus of WAG/Rij rats modelling absence epilepsy. Neuropharmacology, 196 . ISSN 0028-3908

Full content URL: https://doi.org/10.1016/j.neuropharm.2021.108686

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Group I metabotropic glutamate receptor-mediated long-term depression is disrupted in the hippocampus of WAG/Rij rats modelling absence epilepsy
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Abstract

Absence epilepsy is frequently associated with cognitive dysfunction, although the underlying mechanisms are not well understood. Here we report that some forms of hippocampal synaptic plasticity are abnormal in symptomatic Wistar Albino Glaxo/ Rijswijk (WAG/Rij) rats. Metabotropic Glu1/5 receptor-mediated long term depression (LTD) at Schaffer collateral CA1 synapses is significantly reduced in symptomatic, 5-6 months old WAG/Rij rats compared to age-matched non epileptic control rats. There were no significant changes in mGlu1/5-dependent LTD in pre-symptomatic, 4-6 weeks old WAG/Rij rats compared to age matched controls. The reduction in LTD found in symptomatic WAG/Rij rats appears to be specific to only certain forms of synaptic plasticity as long term potentiation (LTP) was unchanged. Immunoblot analysis showed a significant reduction in mGlu5 receptor expression and an increase in pan Homer protein levels with no changes in mGlu1α receptor protein levels in the hippocampus of symptomatic WAG/Rij rats vs non-epileptic control rats. The expression of GluA1 and GluA2 AMPA receptor subunits was also reduced in symptomatic WAG/Rij rats. These findings suggest that abnormalities in hippocampal mGlu5 receptor-dependent synaptic plasticity are associated with the pathological phenotype of WAG/Rij rats. This lays the groundwork for the study of mGlu5 receptors as a candidate drug target for the treatment of cognitive dysfunction linked to absence epilepsy

Keywords:Group I mGlu receptors; hippocampal synaptic plasticity; Absence epilepsy; WAG/Rij rats
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
Divisions:College of Science > School of Pharmacy
ID Code:48914
Deposited On:11 Apr 2022 11:37

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