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Evaluation of the effects of liraglutide on the development of epilepsy and behavioural alterations in two animal models of epileptogenesis

Citraro, R; Iannone, M; Leo, A; De Caro, C; Nesci, V; Tallarico, M; Abdalla, K; ... Russo, E; + view all (2019) Evaluation of the effects of liraglutide on the development of epilepsy and behavioural alterations in two animal models of epileptogenesis. Brain Research Bulletin , 153 pp. 133-142. 10.1016/j.brainresbull.2019.08.001. Green open access

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Abstract

Liraglutide (LIR) is a novel long-lasting glucagon-like peptide-1 (GLP-1) analogue that facilitates insulin signalling and shows also neuroprotective properties in different brain disease models. In this study, we explored the potential antiepileptogenic effects of LIR in two different animal models; namely, the mouse intrahippocampal kainic acid (KA) model of temporal lobe epilepsy and the WAG/Rij rat model of absence epileptogenesis. Moreover, we evaluated LIR effects on comorbidities in various behavioural tests. Mice with kainate-induced epilepsy were treated with LIR (300 g/kg/day s.c.) for 4 weeks after status epilepticus and then evaluated for drug effects on seizure development and behavioural alterations, whereas WAG/Rij rats were treated for 17 weeks (starting at 30 days of age, before seizure onset) with LIR (300 µg/kg/day s.c.) in order to investigate whether an early chronic treatment was able to reduce the development of absence seizures and related comorbidities. Our results indicate that LIR was effective in reducing the development of spontaneous seizures in kainate-induced epilepsy; moreover, in this model, it prevented memory impairment and related anxiety-like behaviour in the open field (OF) test while in the forced swimming test (FST), LIR displayed an apparent pro-depressant effect that was instead related to reduced endurance as confirmed by rotarod test. In contrast, LIR was unable to modify the epileptogenic process underlying the development of absence seizures in WAG/Rij rats while being antidepressant in the FST in this strain. Our results indicate that LIR may represent a promising novel treatment to prevent and treat the epileptogenic process and its associated behavioural and cognitive alterations in some models of convulsive epilepsy characterized by neurodegeneration, since LIR effects are likely secondary to its recognised neuroprotective properties.

Type: Article
Title: Evaluation of the effects of liraglutide on the development of epilepsy and behavioural alterations in two animal models of epileptogenesis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.brainresbull.2019.08.001
Publisher version: https://doi.org/10.1016/j.brainresbull.2019.08.001
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Epileptogenesis; GLP-1 receptor agonist; Kainate-induced seizures; Memory; WAG/Rij rats; Depression
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10079672
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