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ADHD (주의력결핍 과잉행동장애) 생쥐 모델에서의 별아교세포 유래 신경전달물질 분석

Analysis of Gliotransmitters in ADHD Mice

  • 김가연 (단국대학교 분자생물학과) ;
  • 박재원 (단국대학교 분자생물학과) ;
  • 윤보은 (단국대학교 분자생물학과)
  • Kim, Ga-Yeon (Department of Molecular Biology, Dankook University) ;
  • Park, Jaewon (Department of Molecular Biology, Dankook University) ;
  • Yoon, Bo-Eun (Department of Molecular Biology, Dankook University)
  • 투고 : 2017.12.28
  • 심사 : 2018.02.21
  • 발행 : 2018.05.30

초록

ADHD (Attention Deficit/Hyperactivity Disorder)은 4-17세의 아동 및 청소년의 약 10%가 겪는 흔한 신경 발달 장애이지만 그 핵심 기전이 알려져 있지 않은 가운데 관련한 여러 단백질들이 보고되어왔다. 이중 GIT1 (G-protein coupled-receptor kinase interacting protein-1)은 중추신경계에서 dendritic spine formation와 growth에 영향을 미치는 multifunctional adaptor protein으로, GIT1이 제거된 생쥐는 과잉행동, 주의력결핍 그리고 충동성을 보이는 ADHD 증상을 보이게 된다. 이 논문에서는 GIT1 유전자 변형 생쥐를 이용하여 genotype별로 신경교세포의 전달물질(gliotransmitter)을 비교 분석하는 실험을 진행하였다. 그 결과 주요 흥분성 전달물질인 glutamate는 HE (hetero)와 KO (knock-out)의 세포 내에서 WT (wildtype)보다 더 높은 농도로 존재했다. 한편, 억제성 신경전달물질인 GABA와 glycine의 경우 전반적으로 HE에서 가장 많은 함유량을 보였지만 소뇌 세포내의 경우, KO이 WT보다 많은 양을 함유한 것에 비해 대뇌 세포 내에서는 KO보다 WT의 억제성 전달물질 함유량이 높았다. 또한, glutamate와 GABA를 기준으로 흥분성/억제성 비율(excitation/inhibition ratio)을 보았을 때, 소뇌 세포 내/외 모두에서 KO이 가장 높은 수치를 보였고, 대뇌에서는 세포 내/외 모두 HE에서 가장 높은 수치를 보였다. 억제성 신경전달물질인 GABA가 KO의 대뇌 세포 외에서 가장 많은 것으로 보아 GIT1 결손을 보완하기 위해 억제성 물질을 더 많이 분비하거나 또는 과도하게 분비된 GABA를 재흡수하지 못하는 것이라 사료된다. 이는 ADHD 병리기전으로써 기능할 가능성을 제시하며 후속 연구를 통해 해당 기전에 대한 규명이 필요할 것으로 보인다.

Although the core mechanisms of Attention Deficit/Hyperactivity Disorder (ADHD) are unknown, several ADHD-associated proteins have been studied. G-protein - coupled receptor kinase interacting protein-1 (GIT1) is a multifunctional adapter protein that affects neuron growth and dendrite formation. GIT1-deficient mice have shown ADHD-like behavior and also recovered through amphetamine treatment. In this study, gliotransmitters were investigated in both intracellular and extracellular space from GIT1-deficient mice. To measure the amount of gliotransmitters, primary astrocyte cultures were taken from the cerebral and cerebellar cortices of wild (WT), hetero (HE), and knock-out (KO) mice. Major gliotransmitters were analyzed using high-performance liquid chromatography. It was observed that the amount of excitatory and inhibitory gliotransmitters were dependent on genotype and showed a change in excitation/inhibition ratios. Interestingly, the major excitatory gliotransmitter, glutamate, existed at the lowest level in WT mice, but the amount of inhibitory gliotransmitters, gamma-aminobutyric acid (GABA) and glycine, varied depending on brain region. Remarkably, an increased amount of GABA was measured at the intracellular cerebrum in WT mice compared with KO mice. It was presumed that KO mice would secrete more inhibitory gliotransmitters to compensate for GIT1 depletion or else acquire a defect to reuptake-secreted GABA. This may be a possible mechanism for ADHD pathology.

키워드

참고문헌

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