Metabolic Alterations Predispose to Seizure Development in High-Fat Diet-Treated Mice: the Role of Metformin
- PDF / 1,286,541 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 10 Downloads / 186 Views
Metabolic Alterations Predispose to Seizure Development in High-Fat Diet-Treated Mice: the Role of Metformin Valentina Nesci 1 & Emilio Russo 1,2 & Biagio Arcidiacono 1 & Rita Citraro 1 & Martina Tallarico 1 & Andrew Constanti 3 & Antonio Brunetti 1 & Giovambattista De Sarro 1 & Antonio Leo 1 Received: 26 May 2020 / Accepted: 7 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The link between epilepsy and type 2 diabetes (T2DM) and/or metabolic syndrome (MetS) has been poorly investigated. Therefore, we tested whether a high-fat diet (HFD), inducing insulin-resistant diabetes and obesity in mice, would increase susceptibility to develop generalized seizures induced by pentylentetrazole (PTZ) kindling. Furthermore, molecular mechanisms linked to glucose brain transport and the effects of the T2DM antidiabetic drug metformin were also studied along with neuropsychiatric comorbidities. To this aim, two sets of experiments were performed in CD1 mice, in which we firstly evaluated the HFD effects on some metabolic and behavioral parameters in order to have a baseline reference for kindling experiments assessed in the second section of our protocol. We detected that HFD predisposes towards seizure development in the PTZkindling model and this was linked to a reduction in glucose transporter-1 (GLUT-1) expression as observed in GLUT-1 deficiency syndrome in humans but accompanied by a compensatory increase in expression of GLUT-3. While we confirmed that HFD induced neuropsychiatric alterations in the treated mice, it did not change the development of kindling comorbidities. Furthermore, we propose that the beneficial effects of metformin we observed towards seizure development are related to a normalization of both GLUT-1 and GLUT-3 expression levels. Overall, our results support the hypothesis that an altered glycometabolic profile could play a pro-epileptic role in human patients. We therefore recommend that MetS or T2DM should be constantly monitored and possibly avoided in patients with epilepsy, since they could further aggravate this latter condition. Keywords Type 2 diabetes . Metabolic syndrome . Epilepsy . Glucose transporters . Behavioral comorbidities
Introduction A European cohort study has demonstrated that patients with epilepsy (PWE) are at higher risk of comorbid illnesses in comparison with the general population. Predominantly, this risk is Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-02062-6) contains supplementary material, which is available to authorized users. * Emilio Russo [email protected] 1
Science of Health Department, School of Medicine, University “Magna Graecia” of Catanzaro, Viale Europa e Germaneto, 88100 Catanzaro, Italy
2
C.I.S.-Interdepartmental Services Centre of Veterinary for Human and Animal Health, Magna Graecia University of Catanzaro, Viale Europa, Loc. Germaneto, 88100 Catanzaro, Italy
3
Department of Pharmacology, UCL School of Pharmacy, 29/39 Brunswick Square, London, UK
Data Loading...
