WAG/Rij rat model: a resource for the pharmacology of epileptogenesis and related neurological/psychiatric comorbidities
DOI:
https://doi.org/10.31117/neuroscirn.v1i3.22Keywords:
epileptogenesis, absence seizures, comorbidity, depression, cognitive declineAbstract
The discovery of potential antiseizure drugs (ASDs) requires the use of experimental models that can also provide a unique chance for identifying new effective molecules able to prevent and/or cure epilepsy. Most of the preclinical knowledge on epileptogenesis derives from studies performed on post-insult models that are characterized by a recognizable first insult, a silent period lasting until the onset of the first seizure and a chronic period characterized by spontaneous recurrent seizures (SRSs). At odds, genetic models, in which the first insult remains to be identified, have been poorly investigated. Among the genetic models, the WAG/Rij rat was validated as a suitable experimental model of absence epileptogenesis with neuropsychiatric symptomatology, in which, according to our previous hypothesis on SRSs onset, genes could be considered the first ‘insult’ underlying all plastic modifications supporting the occurrences of absence seizures in this strain. In fact, in several genetic models, the initial insult could be described as the mutation leading to epilepsy that, to date, remains to be defined in this strain. The silent period ends at the occurrence of the first SRS, which is approximately at 2-3 months of age in these rats and after that time the chronic phase initiates, in which, absence seizures increase over time underlying likely further epileptogenic processes. In this review, we describe both the features of this experimental model and the effects of several pharmacological treatments against epileptogenesis and its related comorbidities including depressive-like symptoms and cognitive decline.
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Copyright (c) 2019 Antonio Leo, Carmen De Caro, Valentina Nesci, Martina Tallarico, Giovanna Mangano, Ernesto Palma, Michelangelo Iannone, Giovambattista De Sarro, Rita Citraro, Emilio Russo
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