Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Glucocorticoid Regulation of Gene Expression in Hippocampal CA3 and Dentate Gyrus

글루코코티코이드 호르몬에 의한 뇌해마의 CA와 Dentate Gyrus 부분의 유전자 발현 변화

  • Kim, Dong-Sub (School of Applied and Life Science, College of National Resources and Life Science, Pusan National University) ;
  • Ahn, Soon-Cheol (Department of Microbiology and Immunology, School of Medicine, Pusan National University) ;
  • Kim, Young-Jin (Department of Microbiology and Immunology, School of Medicine, Pusan National University) ;
  • Park, Byoung-Keun (Bio21 Center) ;
  • Ahn, Yong-Tae (Korea Basic Science Institute) ;
  • Kim, Ji-Youn (Korea Basic Science Institute) ;
  • Kyoji, Morita (Department of Pharmacolosy, Tokushima University School of Medicine) ;
  • Her, Song (Korea Basic Science Institute)
  • 김동섭 (부산대학교 생명자원과학대학 생명응용과학부) ;
  • 안순철 (부산대학교 의과대학 미생물학교실 및 면역학교실) ;
  • 김영진 (부산대학교 의과대학 미생물학교실 및 면역학교실) ;
  • 박병권 ;
  • 안용태 (한국기초과학지원연구원/춘천센터) ;
  • 김지연 (한국기초과학지원연구원/춘천센터) ;
  • ;
  • 허송욱 (한국기초과학지원연구원/춘천센터)
  • Published : 2007.03.30
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Abstract

Glucocorticoids (GCs) alter metabolism, synaptogenesis, apoptosis, neurogenesis, and dendritic morphology in the hippocampus. To better understand how glucocorticoids regulate these aspects of hippocampal biology, we studied gene expression patterns in the CA3 (Hippocampal pyramidal cell field CA3) and dentate gyrus (DG). Litter-matched Lewis inbred rats treated for 20 days with either 9.5 mg per day sustained-release corticosterone or placebo pellets were compared with high-density oligonucleotide microarray analysis (Rat Neurobiology U34 Arrays, Affymetrix). In placebo-treated rats, 32 genes were expressed at greater levels in CA3 than DG, whereas 3 genes were expressed at great levels in DC than CA3. Regional differences were also apparent in corticosterone-induced changes in the hippocampal transcriptome. Six genes in CA3 and 41 genes in DC were differentially regulated by corticosterone. As per the glucocorticoid effects on gene transcription in the brain, forty three of these genes were upregulated, and 4 genes were downregulated. Genes differentially expressed in hippocampus included those for 13 neurotransmitter proteins, 5 ion channel related proteins, 4 transcription factors, 3 neurotrophic factors, 1 cytokine, 1 apoptosis related protein, and 5 genes involved in synaptogenesis. Interestingly, GCs can have suppressive effects on brain BDNF mRNA transcription, one of the neurotrophic factors. These results indicate the diversity of targets affected by chronic exposure to corticosterone and highlight important regional differences in hippocampal neurobiology.

글루코코르티코이드는 해마 조직에서 대사, 스냅신 형성, apoptosis, 신경세포 생성과 세포에 있어서 수지상의 형태에 영향을 준다. 글루코코르티코이드 호르몬에 의한 해마조직의 생리학적 조절을 이해하기 위하여, CA3와 DG (dentate gyrus)에서 유전자 발현에 대하여 조사하였다. Lewis 쥐에 9.5mg의 코르티코스테론 알약 또는 플라시보 알약을 20일 동안 처리한 후에 올리고머 유전자 칩을 이용하여 유전자 발현을 조사 하였다 (Rat Neurobiology U34 Arrays, Affymetrix). 플라시보 알약을 처리한 쥐에서 32 유전자들이 DG보다 CA3에서 발현이 높았으며, 3개 유전자는 CA3보다 DG에서 높은 발현을 보였다. 코르티코스테론 호르몬 처리에 의한 해마조직의 유전자 발현 형태는 해부학적 구조의 차이를 보였다. 특히, CA3에서 6개의 유전자와 DG에서 41 개의 유전자가 호르몬에 의하여 조절 받았으며, 이중 43개의 유전자가 상승 발현하였으며, 4개의 유전자가 하강 발현 하였다. 이들 유전자를 기능에 의해 분류하면, 13개의 신경전달물질관련 유전자, 5개의 이온채널,4개의 전사인자, 3개의 neurotrophic인자, 1개의 각 사이토카인과 apoptosis관련 유전자, 그리고 5개의 스냅신형성관련 유전자가 해마조직에서 발현의 변화를 보였다. 특히, 스트레스 호르몬에 의하여 CA3에서 BDNF의 감소를 볼 수 있었다. 이러한 결과는 호르몬에 의하여 해마구조의 생리학적인 다양성을 내포 하고 있다.

Keywords

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