Absence seizures (ASs), the most common form of generalized epilepsy, have significant consequences for patients in the form of impaired attention, mood, and social deficits, and the potential for development into generalized tonic-clonic seizures. Althoughmechanistic hypotheses of these paroxysmal oscillations are incomplete, evidence suggests that an increase in extrasynaptic GABAAreceptor (eGABAAR) mediated tonic inhibition in thalamocortical (TC) neurons is sufficient to generate an AS phenotype in multiple rodent models. One of these models is the stargazer (STG) mouse, which has comorbid ataxia and features an early transposon insertion in the voltage-dependent calcium channel (VDCC) subunit gene Cacng2, the protein product of which is known as stargazin. Loss of function in this mutated protein results in aberrant thalamic VDCC regulation and impaired cerebellar AMPA-receptor trafficking,which have been implicated in the absence epileptic and ataxic phenotypes, respectively, of the STG mouse. In TC neurons, eGABAARs invariably contain a δ subunit, and tonic GABAA current in these neurons has thus been shown to be dependent on the expression of that subunit.6 Further, knockout (KO) or suppression of the subunit (by RNA interference) reduces both TC tonic GABAA current and the occurrence of absence seizures in the GHB (γ- hydroxybutyrate) and GAERS (genetic absence epilepsy rats from Strasbourg) models of ASs, respectively. However, the role of the δ subunit and TC tonic GABAA in the development of ASs remains to be demonstrated. Consequently, we investigated whether knockout of the δ subunitin STG mice, via crossbreeding them with δ subunit KO mice, could prevent the development of ASs, thus leading to a “genetic rescue” of the STG epilepsy phenotype.
Genetic rescue of absence seizures / Mccafferty, Cian; Connelly, William M; Celli, Roberta; Ngomba, Richard T; Nicoletti, Ferdinando; Crunelli, Vincenzo. - In: CNS NEUROSCIENCE & THERAPEUTICS. - ISSN 1755-5930. - 24:8(2018), pp. 745-748. [10.1111/cns.12858]
|Titolo:||Genetic rescue of absence seizures|
|Data di pubblicazione:||2018|
|Citazione:||Genetic rescue of absence seizures / Mccafferty, Cian; Connelly, William M; Celli, Roberta; Ngomba, Richard T; Nicoletti, Ferdinando; Crunelli, Vincenzo. - In: CNS NEUROSCIENCE & THERAPEUTICS. - ISSN 1755-5930. - 24:8(2018), pp. 745-748. [10.1111/cns.12858]|
|Appartiene alla tipologia:||01a Articolo in rivista|