Effects of the T-type calcium channel CaV3.2 R1584P mutation on absence seizure susceptibility in GAERS and NEC congenic rats models

• DOI: 10.1016/j.nbd.2023.106217
• Publication Date: 2023-06-28T17:50:01Z
• Authors: Pablo M. Casillas...; Runxuan Lin; Rui Li; Nanditha M. Nanda...; Georgia Dawson; Emma L. Braine; Benoît Martin; Kim L. Powell; Terence J. O'Brien
• Keywords: Congenic

Low-voltage-activated or T-type Ca2+ channels play a key role in the generation of seizures absence epilepsy. We have described homozygous, gain function substitution mutation (R1584P) CaV3.2 channel gene (Cacna1h) Genetic Absence Epilepsy Rats from Strasbourg (GAERS). The non-epileptic control (NEC) rats, derived same original Wistar strains as GAERS but selectively in-breed not to express seizures, are null for R1584P mutation. To study effects this rats who otherwise NEC genetic background, we bred congenic GAERS-Cacna1hNEC (GAERS mutation) and NEC-Cacna1hGAERS (NEC homozygous evaluated seizure behavioral phenotype these comparison strains.To evaluate expression strains, EEG electrodes were implanted NEC, GAERS, without mutation, with rats. In first study, continuous recordings acquired week 4 (when begin develop GAERS) 14 age display hundreds per day). second during young (6 weeks age) adulthood (16 NEC-Cacna1hGAERS. Open field test (OFT) sucrose preference (SPT) performed anxiety-like depressive-like behavior, respectively. This was followed by at 18 quantify spike-wave discharge (SWD) cycle frequency. At end whole thalamus collected calcium mRNA analysis.GAERS had significantly shorter latency an increased number day compared GAERS-Cacna1hNEC. On other hand, presence enough generate spontaneous their seizure-resistant background. 6 16-week-old showed behavior OFT, contrast Results SPT that developed GAERS-Cacna1hNEC, Analysis day, total duration higher frequency SWD relative However, average different between strains. Quantitative real-time PCR isoform ratio + 25/-25 splice variants GAERS-Cacna1hNEC.The data demonstrate isolation on background insufficient can cause even provides evidence acts modulator development expression, SPT, anxiety model