Kanaumi Takeshi, Takashima Sachio, Iwasaki Hiroshi, Itoh Masayuki, Mitsudome Akihisa, Hirose Shinichi
Department of Pediatrics, School of Medicine, Fukuoka University, 45-1, 7-chome Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Brain Dev. 2008 May;30(5):362-9. doi: 10.1016/j.braindev.2007.11.003. Epub 2007 Dec 31.
Several mutations of KCNQ2 and KCNQ3 are considered to be associated with benign familial neonatal convulsions (BFNC). BFNC is characterized by seizures starting within several days of life and spontaneous remission within weeks to months. KCNQ channel is a heteromeric voltage-dependent potassium channel consisting of KCNQ2 and KCNQ3 subunits. To clarify the age-dependent etiology of BFNC, we examined the developmental changes in KCNQ2 and KCNQ3 expression in human hippocampus, temporal lobe, cerebellum and medulla oblongata obtained from 23 subjects who died at 22 gestation weeks to adulthood. Formalin-fixed and paraffin-embedded specimens were used for immunohistochemistry. Unique developmental changes in KCNQ2 and KCNQ3 were found in each region. A high expression of KCNQ2 was identified in the hippocampus, temporal cortex, cerebellar cortex and medulla oblongata in fetal life, but such expression decreased after birth. The expression of KCNQ3 increased in late fetal life to infancy. Simultaneous and high expressions of KCNQ2 and KCNQ3 were observed in each region from late fetal life to early infancy, coinciding with the time when BFNC occurs. Such coexpression may contribute to the pathogenesis of BFNC.
KCNQ2和KCNQ3的几种突变被认为与良性家族性新生儿惊厥（BFNC）相关。BFNC的特征是在出生后几天内开始发作，并在数周或数月内自发缓解。KCNQ通道是一种由KCNQ2和KCNQ3亚基组成的异源电压依赖性钾通道。为了阐明BFNC的年龄依赖性病因，我们研究了从22孕周至成年期死亡的23名受试者获取的人类海马体、颞叶、小脑和延髓中KCNQ2和KCNQ3表达的发育变化。福尔马林固定和石蜡包埋的标本用于免疫组织化学。在每个区域都发现了KCNQ2和KCNQ3独特的发育变化。在胎儿期，海马体、颞叶皮质、小脑皮质和延髓中KCNQ2表达较高，但出生后这种表达下降。KCNQ3的表达在胎儿晚期至婴儿期增加。从胎儿晚期到婴儿早期，在每个区域都观察到KCNQ2和KCNQ3同时高表达，这与BFNC发生的时间一致。这种共表达可能有助于BFNC的发病机制。
