Cho Inja, Cho Yang-Je, Kim Hyun-Woo, Heo Kyung, Lee Byung-In, Kim Won-Joo
Department of Neurology and Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Korea ; Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Korea.
Department of Neurology and Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Korea.
J Epilepsy Res. 2014 Jun 30;4(1):7-13. doi: 10.14581/jer.14002. eCollection 2014 Jun.
Neurosteroids exert their antiepileptic effects via GABAA and NMDA receptors. Another cell death mechanism is excessive Ca(2+) influx into cells. Calbindin-D28k (CB) is a protein that modulates intracellular Ca(2+) in the nervous system. We evaluated whether androsterone up-regulates the expression of CB and has a neuroprotective effect by controlling Ca(2+) after pilocarpine-induced status epilepticus (SE) in mice.
SE was induced in ICR mice by injection of pilocarpine. Two hours after SE, mice were treated intraperitoneally (i.p.) with androsterone (100-200 mg/kg) or vehicle, and compared with other control groups. Two days after injection, immunohistochemical staining for CB was performed using a hippocampal slice from each mice group. We also used cresyl violet staining to compare changes in hippocampal structures.
Two days after pilocarpine-induced SE, androsterone increased the expression of CB in the hippocampus compared with control SE mice. The number of CB-positive cells was 1±0.4 cells/mm(3) in pilocarpine-only group, 14±1.1 cells/mm(3) in pilocarpine plus androsterone 100 mg group and 29±2.5 cells/mm(3) in pilocarpine plus androsterone 200 mg group (p<0.001).
These results suggest that the neuroprotective effect of androsterone after pilocarpine- induced SE may be mediated by an increased expression of CB.
神经甾体通过GABAA和NMDA受体发挥抗癫痫作用。另一种细胞死亡机制是细胞内过量的Ca(2+)内流。钙结合蛋白-D28k（CB）是一种调节神经系统细胞内Ca(2+)的蛋白质。我们评估了雄甾酮是否上调CB的表达，并在毛果芸香碱诱导的小鼠癫痫持续状态（SE）后通过控制Ca(2+)发挥神经保护作用。
通过注射毛果芸香碱在ICR小鼠中诱导SE。SE后两小时，小鼠腹腔注射（i.p.）雄甾酮（100 - 200 mg/kg）或溶剂，并与其他对照组进行比较。注射两天后，使用每组小鼠的海马切片进行CB的免疫组织化学染色。我们还使用甲酚紫染色来比较海马结构的变化。
毛果芸香碱诱导SE两天后，与对照SE小鼠相比，雄甾酮增加了海马中CB的表达。仅用毛果芸香碱组的CB阳性细胞数为1±0.4个细胞/mm(3)，毛果芸香碱加100 mg雄甾酮组为14±1.1个细胞/mm(3)，毛果芸香碱加200 mg雄甾酮组为29±2.5个细胞/mm(3)（p<0.001）。
这些结果表明，毛果芸香碱诱导SE后雄甾酮的神经保护作用可能是由CB表达增加介导的。
