Protective effects of some statins on epileptogenesis and depressive‐like behavior in <scp>WAG</scp>/Rij rats, a genetic animal model of absence epilepsy

Citraro, Rita; Chimirri, Serafina; Aiello, Rossana; Gallelli, Luca; Trimboli, Francesca; Britti, Domenico; Sarro, Giovambattista De; Russo, Emilio

doi:10.1111/epi.12686

Cited by 54 publications

(61 citation statements)

References 49 publications

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“…The studies of lovastatin and its analogs have been reported in several seizure models including audiogenic models in rodent and several observational studies in human (Banach et al 2014; Citraro et al 2014; Russo et al 2013; Scicchitano et al 2015). While the efficacy of seizure suppression varies from study to study, the anticonvulsant effect has been documented for lovastatin and other analogs.…”

Section: Discussionmentioning

confidence: 99%

Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model

Chung

Bey

Towers

et al. 2018

Neurobiology of Disease

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Epilepsy is prevalent and often medically intractable in Angelman syndrome (AS). AS mouse model (Ube3am−/p+) shows reduced excitatory neurotransmission but lower seizure threshold. The neural mechanism linking the synaptic dysfunction to the seizure remains elusive. We show that the local circuits of Ube3am−/p+ in vitro are hyperexcitable and display a unique epileptiform activity, a phenomenon that is reminiscent of the finding in fragile X syndrome (FXS) mouse model. Similar to the FXS model, lovastatin suppressed the epileptiform activity and audiogenic seizures in Ube3am−/p+. The in vitro model of Ube3am−/p+ is valuable for dissection of neural mechanism and epilepsy drug screening in vivo.

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Section: Discussionmentioning

confidence: 99%

Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model

Chung

Bey

Towers

et al. 2018

Neurobiology of Disease

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“…During this period, animals were weighed weekly every Monday between 9:00 and 11:00. Furthermore, particular attention was paid to the possible appearance of any obvious drug induced side-effects [47].…”

Section: For Subchronic Treatmentmentioning

confidence: 99%

Comparative Analysis of the Treatment of Chronic Antipsychotic Drugs on Epileptic Susceptibility in Genetically Epilepsy-prone Rats

et al. 2015

Self Cite

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Antipsychotic drugs (APs) are of great benefit in several psychiatric disorders, but they can be associated with various adverse effects, including seizures. To investigate the effects of chronic antipsychotic treatment on seizure susceptibility in genetically epilepsy-prone rats, some APs were administered for 7 weeks, and seizure susceptibility (audiogenic seizures) was evaluated once a week during treatment and for 5 weeks after drug withdrawal. Furthermore, acute and subchronic (5-day treatment) effects were also measured. Rats received haloperidol (0.2-1.0 mg/kg), clozapine (1-5 mg/kg), risperidone (0.03-0.50 mg/kg), quetiapine (2-10 mg/kg), aripriprazole (0.2-1.0 mg/kg), and olanzapine (0.13-0.66 mg/kg), and tested according to treatment duration. Acute administration of APs had no effect on seizures, whereas, after regular treatment, aripiprazole reduced seizure severity; haloperidol had no effects and all other APs increased seizure severity. In chronically treated rats, clozapine showed the most marked proconvulsant effects, followed by risperidone and olanzapine. Quetiapine and haloperidol had only modest effects, and aripiprazole was anticonvulsant. Finally, the proconvulsant effects lasted at least 2-3 weeks after treatment suspension; for aripiprazole, a proconvulsant rebound effect was observed. Taken together, these results indicate and confirm that APs might have the potential to increase the severity of audiogenic seizures but that aripiprazole may exert anticonvulsant effects. The use of APs in patients, particularly in patients with epilepsy, should be monitored for seizure occurrence, including during the time after cessation of therapy. Further studies will determine whether aripiprazole really has a potential as an anticonvulsant drug and might also be clinically relevant for epileptic patients with psychiatric comorbidities.

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“…As HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, statins can effectively decrease blood cholesterol levels 8 . Recently, SMV has been reported to show some cholesterol-independent effects that include anti-inflammatory, anti-oxidative and neuro-protective properties 9 .…”

Section: Introductionmentioning

confidence: 99%

Simvastatin and Bezafibrate ameliorate Emotional disorder Induced by High fat diet in C57BL/6 mice

Wang

Zhou

Liu

et al. 2017

Sci Rep

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High fat diet (HFD)-induced metabolic disorders may lead to emotional disorders. This study aimed to explore the effect of simvastatin (SMV) and bezafibrate (BZ) on improving HFD-induced emotional changes, and tried to identify their different mechanisms. The intraperitoneal glucose tolerance test (IPGTT) was used to evaluate glucose control ability; and behavior tests including open field tests (OFT), forced swimming tests (FST), tail suspension tests (TST) and sucrose preference (SPT), were then performed to evaluate emotional changes. Serum samples were collected for the LC-MS based metabolomics analysis to explore the emotional-related differential compounds; we then evaluated the effect of the drugs. The abnormal serum metabolic profiling and emotional changes caused by HFD in mice was alleviated by SMV treatment, whereas BZ only affected the emotional disorder. The improvement of cannabinoid analogues and then produced influences on the endocannabinoid system, which may be a potential mechanism SMV action. BZ promoted tryptophan-serotonin pathway and inhibited tryptophan-kynurenine pathway, which may be its mechanism of action. Here, we proposed a shed light on the biological mechanisms underlying the observed effects, and identified an important drug candidate for the treatment of emotional disorders induced by HFD.

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Protective effects of some statins on epileptogenesis and depressive‐like behavior in WAG/Rij rats, a genetic animal model of absence epilepsy

Cited by 54 publications

References 49 publications

Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model

Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model

Comparative Analysis of the Treatment of Chronic Antipsychotic Drugs on Epileptic Susceptibility in Genetically Epilepsy-prone Rats

Simvastatin and Bezafibrate ameliorate Emotional disorder Induced by High fat diet in C57BL/6 mice

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