SOD1G93A transgenic mice의 중추신경계에서glycogen synthase kinase (GSK) 3β의 분포에 관한면역조직화학적 연구
Immunohistochemical Study on the Distribution of Glycogen Synthase Kinase (GSK) 3β in theCentral Nervous System of SOD1G93A Transgenic Mice
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본 연구에서 glycogen synthase kinase (GSK) 3β가 근위축성측삭경화증(ALS)의 발병과 진행과정에서 어 떤 영향을 미치는지 알아보고자 하였다. 실험동물로는 ALS의 in vivo model인 SOD1G93A transgenic mice를 이용하였고, 면역조직화학적 방법을 사용하여 GSK3β의 발현변화를 연구하였다. 연구결과, 증상을 보이는 SOD1G93A transgenic mice의 척수, 뇌줄기, 소뇌의 신경세포에서 증가된 GSK3β 면역염 색성을 나타냈다. 이와 대조적으로, 증상을 보이기 전인 8주령과 13주령의 SOD1G93A transgenic mice에서는 GSK3β 면역염색성을 거의 관찰할 수 없었다. 본 연구결과는 GSK3가 ALS의 apoptosis와 관련된 변화의 조절인자로서 작용할 가능성을 제시하였고, 또한 ALS의 발병과 진행과정에서 다르게 작용할 가능성도 보여주었다. 그러나 이러한 변화에 대한 정확한 기능적인 의미에 대해서는 더 많은 연구가 이루어져야 할 것이다.
Abstract
In the present study, we investigated influences of glycogen synthase kinase (GSK) 3β on the development and/or progression of amyotrophic lateral sclerosis (ALS). We used transgenic mice expressing a human Cu/Zn superoxide dismutase mutant (SOD1G93A) as an in vivo model of ALS and examined expressional changes of GSK3β immunohistochemically in the spinal cord, brain stem and cerebellum. With these experiments we demonstrate that the neurons in these regions of symptomatic SOD1G93A transgenic mice showed increased GSK3β immunoreactivities compared with wild-type SOD1 transgenic mice. In contrast to symptomatic SOD1G93A transgenic mice, few GSK3β immunoreactivity changes were detected in 8w- and 13w-old presymptomatic SOD1G93A transgenic mice. These data suggest the possibility that GSK3 functions as a modulating factor of apoptosis-related alterations in ALS and that GSK3β exert differential functions in the development and/or progression of ALS. But the exact functional significances of these changes require further elucidation.
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