Abstracts

Rationale: The aim of this study will verify the preventative effects of increasing the expression of leucine-rich alpha2 glycoprotein (LRG1) in the brain regarding the decline of cognitive function caused by epileptic seizures using an animal model of temporal lobe epilepsy through a pilocarpine-induced epileptic state.  Methods: Electrophysiological and molecular biological analyses were performed on adult secondary epileptogenic formation using an animal model of TLE induced with pilocarpine utilizing CAG-loxP-GFP-loxP-LRG1 transgenic mice (LRG-Tg). Pilocarpine was administered to 8 to 10-week-old mice (LRG-Tg or wild type) to create a model of TLE. Eight weeks after status epilepticus, cognitive behavioral tests were administered and long-term potentiation (LTP) in the CA1 region of the hippocampus was measured in epilepsy and non-epilepsy groups. Immunostaining was carried out with hippocampal tissue slices to confirm neural dropout and the expression of cyclic AMP response element-binding protein (CREB).  Results: The cognitive behavioral experiments indicated a significant decline in cognitive function 8 weeks after status epilepticus in wild type mice and significant reduction in LTP was confirmed through ANOVA. Meanwhile, LTP reduction was not observed after status epilepticus in the LRG-Tg mice. Neural dropout in the CA1 region of the hippocampus after status epilepticus was particularly marked in the wild type mice.  Conclusions: LRG1 expression in the hippocampus was confirmed to suppress nerve cell firing and prevent cognitive function decline after status epilepticus.  Funding: This work was supported in part by the Grant-in-Aid for Scientific Research (grant number: 16KK0187, C # 17K10908) from the Japan Society for the Promotion of Science.