| Popis: |
Background The ARHGEF15 gene encodes the Rho guanine nucleotide exchange factor 15. Although multiple evidence indicates that ARHGEF15 may be related to epilepsy, it is not clear what role it plays. Methods Subjects were homozygous ARHGEF15 knockout (E5−/−) mice, wild-type (WT) mice, Cre-positive homozygous human ARHGEF15 conditional knock-in (E5CKI/CKI•Cre+) mice which can overexpress human Ephexin5 in the forebrain, and Cre-positive (E5WT/WT•Cre+) mice. Models with epileptic seizures were established by intraperitoneal injection of pentylenetetrazol (PTZ) in 60 mg/kg, and seizures were recorded by video. Then 7 indexes were counted, including “maximum seizure level”, “seizure level classification”, “tonic-clonic seizure or not”, “latency of tonic-clonic seizure”, “number of times of tonic-clonic seizure”, “total duration of tonic-clonic seizure”, and “dead or not”. Western blot was used to detect Ephexin5, RhoA, p-RhoA, ROCK2, and p-ROCK2 in WT mice and E5−/− mice. Results Compared with WT mice, E5−/− mice had a shorter “total duration of tonic-clonic seizure”. For levels of RhoA, p-RhoA, ROCK2 and p-ROCK2 in the adult hippocampus, there was no significant difference between WT and E5−/−. The level of Ephexin5 was high in the whole brain tissue of 2-day-old WT mice, and an extremely low expression of Ephexin5 was detected in the brain tissue of E5−/− mice of the same age. There was no significant difference between E5CKI/CKI•Cre + mice and E5WT/WT•Cre + mice in seizures. Conclusions ARHGEF15 knockout can decrease the “duration of tonic-clonic seizure” in adult mice with epileptic seizures induced by PTZ. ARHGEF15 knockout did not affect the expression of the RhoA-ROCK2 pathway in the hippocampus of adult mice, which probably attributed to no expression of Ephexin5 in the hippocampus of adult mice. The overexpression of human Ephexin5 in the forebrain has no significant effect on the behavior of epileptic seizures induced by PTZ in adult mice. |
