| First Author | Majewski L | Year | 2019 |
| Journal | Int J Mol Sci | Volume | 20 |
| Issue | 22 | PubMed ID | 31698854 |
| Mgi Jnum | J:290141 | Mgi Id | MGI:6435315 |
| Doi | 10.3390/ijms20225539 | Citation | Majewski L, et al. (2019) Changes in Calcium Homeostasis and Gene Expression Implicated in Epilepsy in Hippocampi of Mice Overexpressing ORAI1. Int J Mol Sci 20(22):5539 |
| abstractText | Previously, we showed that the overexpression of ORAI1 calcium channel in neurons of murine brain led to spontaneous occurrence of seizure-like events in aged animals of transgenic line FVB/NJ-Tg(ORAI1)Ibd (Nencki Institute of Experimental Biology). We aimed to identify the mechanism that is responsible for this phenomenon. Using a modified Ca(2+)-addback assay in the CA1 region of acute hippocampal slices and FURA-2 acetomethyl ester (AM) Ca(2+) indicator, we found that overexpression of ORAI1 in neurons led to altered Ca(2+) response. Next, by RNA sequencing (RNAseq) we identified a set of genes, whose expression was changed in our transgenic animals. These data were validated using customized real-time PCR assays and digital droplet PCR (ddPCR) ddPCR. Using real-time PCR, up-regulation of hairy and enhancer of split-5 (Hes-5) gene and down-regulation of aristaless related homeobox (Arx), doublecortin-like kinase 1 (Dclk1), and cyclin-dependent kinase-like 5 (Cdkl5, also known as serine/threonine kinase 9 (Stk9)) genes were found. Digital droplet PCR (ddPCR) analysis revealed down-regulation of Arx. In humans, ARX, DCLK1, and CDLK5 were shown to be mutated in some rare epilepsy-associated disorders. We conclude that the occurrence of seizure-like events in aged mice overexpressing ORAI1 might be due to the down-regulation of Arx, and possibly of Cdkl5 and Dclk1 genes. |
