Comprehensive research of MMP gene in an animal model of epileptic seizure

在本研究中，我们研究了基质金属蛋白酶（MMP）-9在戊四氮（PTZ）诱导的小鼠点燃癫痫发作中的作用。PTZ（40 mg/kg）重复处理产生点燃癫痫发作，这是伴随着增强MMP-9活性和表达在海马。单次给药PTZ（60 mg/kg）后，在全身强直性发作小鼠的大脑中没有观察到MMP-9活性的变化。MMP-9与神经元标记物NeuN和胶质细胞标记物GFAP在点燃的小鼠海马的齿状回中共定位。地西泮或MK-801与PTZ联合给药可抑制点燃的发展和海马中MMP-9水平的增加。与野生型小鼠相比，在MMP-9^（-/-）>小鼠中观察到对重复PTZ治疗的点燃癫痫发作进展的显著抑制，该观察结果伴随着成熟脑源性神经营养因子（BDNF）的海马水平降低，尽管BDNF mRNA水平相似。这些发现表明，MMP-9参与了点燃小鼠的行为表型的进展，由于在海马中的pro-BDNF转化为成熟的BDNF。

In the present study, we investigated the role of matrix metalloproteinase (MMP)-9 in the development of pentylenetetrazole (PTZ)-induced kindled seizure in mice. Repeated treatment with PTZ (40 mg/kg) produced kindled seizure, which was accompanied by enhanced MMP-9 activity and expression in the hippocampus. No change in MMP-9 activity was observed in the hippocampi of mice with generalized tonic seizure following single administration of PTZ (60 mg/kg). MMP-9 colocalized with the neuronal marker NeuN and the glial marker GFAP in the dentate gyrus of the kindled mouse hippocampus. Coadministration of diazepam or MK-801 with PTZ inhibited the development of kindling and the increased MMP-9 levels in the hippocampus. Marked suppression of kindled seizure progression in response to repeated PTZ treatment was observed in MMP-9^<(-/-)> mice compared with wild-type mice, an observation that was accompanied by decreased hippocampal levels of mature brain-derived neurotrophic factor (BDNF) despite similar BDNF mRNA levels. These findings suggest that MMP-9 is involved in progression of behavioral phenotypes in kindled mice owing to conversion of pro-BDNF to mature BDNF in the hippocampus.