Katsumori H, Hashimoto K, Tomitaka S, Osawa M, Minabe Y
Division of Cortical Function Disorders, National Institute of Neuroscience, Tokyo, Japan.
Neurosci Lett. 1997 Apr 11;225(3):149-52. doi: 10.1016/s0304-3940(97)00203-6.
We examined the effects of antisense oligodeoxynucleotides (ODNs) to c-fos mRNA on hippocampal partial seizures in rats. As control, sense and scrambled control ODNs were also tested. Each ODN (10 nmol/10 microliters) was injected into the lateral ventricles for 2 consecutive days. Fifteen hours after the last injection, electrical stimulation was delivered to assess the effects on after discharge threshold and afterdischarge duration (ADD). One hour after seizures, c-Fos and Jun-B immunocytochemistries were performed. Antisense ODNs significantly decreased ADD and control ODNs failed to change any parameters. In the antisense ODNs group, c-Fos expression occurred ipsilateral to the stimulation site in dentate granule cells, while Jun-B expression was seen bilaterally. In the majority of control ODNs animals, c-Fos and Jun-B expression in dentate granule cells occurred bilaterally. These findings suggest that the injection of antisense ODNs selectively inhibit contralateral c-Fos expression and that c-fos plays a key role in hippocampal excitability and seizure expression during hippocampal partial seizures.
我们研究了针对c-fos mRNA的反义寡脱氧核苷酸(ODNs)对大鼠海马局部癫痫发作的影响。作为对照,还测试了正义和乱序对照ODNs。将每种ODN(10 nmol/10微升)连续2天注入侧脑室。最后一次注射后15小时,进行电刺激以评估对放电阈值和放电后持续时间(ADD)的影响。癫痫发作后1小时,进行c-Fos和Jun-B免疫细胞化学检测。反义ODNs显著降低了ADD,而对照ODNs未能改变任何参数。在反义ODNs组中,齿状颗粒细胞中c-Fos表达出现在刺激部位的同侧,而Jun-B表达则双侧可见。在大多数对照ODNs动物中,齿状颗粒细胞中的c-Fos和Jun-B表达双侧出现。这些发现表明,注射反义ODNs可选择性抑制对侧c-Fos表达,并且c-fos在海马局部癫痫发作期间的海马兴奋性和癫痫发作表达中起关键作用。