장기간 플루세틴 처리에 의한 흰쥐 해마에서의 NCAM140 유전자 발현의 증가
Chronic Treatment of Fluoxetine Increases Expression of NCAM140 in the Rat Hippocampus
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목 적 : 흰쥐 해마에서 보고된 항우울제의 기전 대부분은 신경돌기 성장 및 신경세포 생존의 증가에 있다. Neural cell adhesion molecule 140 (NCAM 140)은 세포-세포접착, 신경돌기 성장, 및 시냅스 가소성을 증가시키는 역할을 담당하고 있다. 본 연구는 흰쥐 해마에 장기간 플루세틴 처리가 NACM140 발현과 NCAM140 매개로 인한 세포내 신호전달과정의 하부에 위치한 phosphorelated cyclicAMP responsive element binding protein (pCREB) 활성화와의 관련성을 규명하고자 하였다. 방 법 : 흰쥐에 플루세틴 (10 mg/kg)을 5일 동안 (단기간) 및 14일 동안 (장기간) 투여하였다. 흰쥐 해마로부터 RNA와 단백질을 각각 확보하였다. 실시간 RT-PCR을 수행하여 NCAM140 유전자의 발현을 분석하였고, 웨스턴 블롯 분석으로 CREB의 인산화 정도를 분석하였다. 결 과 : 플루세틴을 장기간 투여한 쥐 해마에서는 대조군에 비해 NCAM140 유전자의 발현이 1.3 배 증가하였다. 또한, 플루세틴을 장기간 투여한 쥐 해마에서 pCREB 활성이 대조군에 비해 4 배 증가하였다. 결 론 : 장기간 플루세틴을 투여할 경우 흰쥐 해마에서 NCAM140 유전자 발현과 pCREB 활성이 증가하였다. 본 연구결과는 NCAM140과 pCREB이 신경돌기 성장과 신경세포의 생존을 촉진시키는 기전이 항우울제의 임상적 효능에 참여하는 것으로 보인다.
Abstract
Objective : Most of the mechanisms reported for antidepressant drugs are the enhancement of neurite outgrowth and neuronal survival in the rat hippocampus. Neural cell adhesion molecule 140 (NCAM140) has been implicated as having a role in cell-cell adhesion, neurite outgrowth, and synaptic plasticity. In this report, we have performed to elucidate a correlation among chronic antidepressant treatments, NCAM140 expression, and activation of phosphorylated cyclicAMP responsive element binding protein (pCREB) which is a downstream molecule of NCAM140-mediated intracellular signaling pathway in the rat hippocampus. Methods : Fluoxetine (10 mg/kg) was injected acutely (daily injection for 5 days) or chronically (daily injection for 14 days) in adult rats. RNA and protein were extracted from the rat hippocampus, respectively. Real-time RT-PCR was performed to analyze the expression pattern of NCAM140 gene and western blot analyses for the activation of the phosphorylation ratio of CREB. Results : Chronic fluoxetine treatments increased NCAM140 expression 1.3 times higher than control in rat hippocampus. pCREB immunoreactivity in the rat hippocampus with chronic fluoxetine treatment was increased 4.0 times higher than that of control. Conclusion : Chronic fluoxetine treatment increased NCAM140 expression and pCREB activity in the rat hippocampus. Our data suggest that NCAM140 and pCREB may participate in the clinical efficacy of antidepressants promoting the neurite outgrowth and neuronal survival.
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