Group I metabotropic glutamate receptor-mediated long term depression is disrupted in the hippocampus of WAG/Rij rats modelling absence epilepsy. (15th September 2021)

• Record Type: Journal Article
• Authors: Di Cicco, Gabriele; Marzano, Emanuela; Iacovelli, Luisa; Celli, Roberta; van Luijtelaar, Gilles; Nicoletti, Ferdinando; Ngomba, Richard T.; Wall, Mark J.
• Is Part Of: Neuropharmacology. Volume 196(2021)
• Publication Date: 2021-09-15
• Subjects: Group I mGlu receptors -- Hippocampal synaptic plasticity -- Absence epilepsy -- WAG/Rij rats; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2021.108686
• Languages: English
• ISSNs: 0028-3908

Abstract

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 Glu 1/5 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 changes in LTD found in symptomatic WAG/Rij forms are not indicative of general deficits in all forms of synaptic plasticity as long term potentiation (LTP) was unchanged. Immunoblot analysis of hippocampal tissue showed a significant reduction in mGlu5 receptor expression, a trend to an increase in pan Homer protein levels and a decrease in GluA1 receptor expression in the hippocampus of symptomatic WAG/Rij rats vs non-epileptic control rats. There were no changes in mGlu1α receptor or GluA2 protein levels. 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. Highlights: mGlu1/5 receptor-mediated long-term depression (LTD) at SC-CA1 synapses is significantly reduced in symptomatic WAG/Rij rats. Variations in expression of mGlu5 receptors and Homer proteins in WAG/Rij rats might contribute to the deficits in LTD. No difference in mGlu receptor-mediated LTD between pre-symptomatic and age matched control Wistar rats. There were no changes in NMDA receptor-dependent LTP in WAG/Rij rats compared to age matched control Wistar rats. Hippocampal mGlu5 receptor-dependent synaptic plasticity are associated with the pathological phenotype of WAG/Rij rats.