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  • 한국과학기술정보연구원(KISTI) 서울분원 대회의실(별관 3층)
  • 2024년 07월 03일(수) 13:30
 

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만성스트레스 우울증 동물 모델에서 경두개자기자극이 해마 시냅스 가소성에 미치는 영향

Effects of rTMS on the hippocampal plasticity in the chronic mild stress model of depression

한국심리학회지: 인지 및 생물 / The Korean Journal of Cognitive and Biological Psychology, (P)1226-9654; (E)2733-466X
2006, v.18 no.4, pp.339-353
김은주 (제주한라대학교)
김운령 (고려대학교)
이연경 (고려대학교)
최준식 (고려대학교)
박은혜 (New York University)
김현택 (고려대학교)
박순권 (고려대학교)
  • 다운로드 수
  • 조회수

초록

경두개자기자극(repetitive transcranial magnetic stimulation: rTMS)은 최근 주요우울증 치료에 이용될 수 있는 가능성이 대두되고 있으나, 이 자극이 작용하는 세포 수준에서의 생리학적 기전은 아직 거의 알려져 있지 않다. 본 연구에서는 rTMS의 작용기전을 세포 수준에서 알아보기 위해 rTMS가 동물의 전기생리학적 변화에 미치는 영향을 검사하였고, 이 효과를 우울증의 전통적 자극 기법인 전기경련충격(electroconvulsive shock: ECS)과 항우울제 중 하나인 fluoxetine과 비교하여 보았다. 수컷 Wistar 쥐를 우울증 동물 모델인 경미한 만성스트레스 (chronic mild stress: CMS) 모델에 6주 동안 노출시켰고, 동물이 자당용액을 섭취하는 양을 측정하여 우울증의 행동적 증상인 무쾌감증(anhedonia)을 검사하였다. CMS에 노출된 동물과 비처치 집단 (NAIVE)의 동물 사이에 자당용액 섭취량에서 통계적으로 유의한 차이가 나타났다. 무쾌감증을 확인한 후, CMS에 노출되었던 동물을 다음의 네 집단으로 나누어 2주 동안 CMS와 함께 처치하였다: rTMS 처치집단(rTMS), 모의 rTMS 처치집단 (SHAM), ECS 처치집단(ECS), fluoxetine 처치집단(FLX). 2주간의 각 처치가 종결된 후, 동물을 마취하여 관통로-치상핵 시냅스에서 장기상승작용(long term potentiation: LTP)을 in vivo로 유도하였고, 흥분성 시냅스후 장전위 (fEPSP)를 기록하였다. NAIVE 집단에 비하여 SHAM 집단과 FLX 집단에서는 LTP가 거의 유도되지 않았다. 그러나, rTMS를 처치한 쥐에서는 LTP가 NAIVE 집단의 수준을 보여 LTP 손상이 일어나지 않은 것을 확인하였다. rTMS 집단에서 LTP 손상이 일어나지 않은 것에 반해, ECS 집단에서는 LTP의 감소 경향이 있었으며, NAIVE 동물과 통계적으로 경미한 차이를 보였다. 이러한 결과는 rTMS가 CMS 처치에 의해 야기될 수 있는 시냅스 효율성의 손상을 보호함으로써 해마 뉴런의 정상적인 전기생리학적 현상을 손상시키지 않으며, rTMS의 항우울 효과는 이러한 시냅스 가소성의 보호 효과를 매개로 할 가능성이 있음을 시사한다.

keywords
repetitive transcranial magnetic stimulation (rTMS), depression, chronic mild stress (CMS), long-term, 경두개자기자극(rTMS), 우울증, 만성스트레스(CMS), 장기상승작용(LTP), 전기경련충격(ECS)

Abstract

Despite its therapeutic success in treating major depression, little is known about the mechanism by which repetitive transcranial magnetic stimulation (rTMS) alters physiological responses of neurons. To elucidate cellular processes underlying rTMS, we compared the effect of rTMS on hippocampal long-term potentiation (LTP) with those of electroconvulsive shock (ECS) and fluoxetine. Male Wistar rats were subjected to chronic mild stress (CMS) regimen, an animal model of depression, for six weeks. Anhedonia, a behavioral symptom of depression, was tested by measuring sucrose consumptions. There was a significant difference in sucrose intake between nave and CMS-exposed animals. The rats were then treated with one of the three conditions: rTMS (rTMS), sham rTMS (SHAM), ECS (ECS), or fluoxetine (FLX) for two weeks. Following two weeks of treatments with rTMS, sham rTMS, ECS, or fluoxetine, they were anesthetized and LTP was induced in vivo in the perforant path-dentate gyrus synapses. Field excitatory postsynaptic potentials (fEPSP) were monitored for 50 min after the LTP induction. LTP induction was impaired in CMS (sham rTMS) and FLX group compared to the nave control group. The potentiated fEPSP of the ECS group was marginally different from that of NAVE group, showing a trend toward impaired LTP. On the other hand, LTP was recovered to the level of nave animals in rats treated with rTMS. These results suggest that rTMS has a rescuing effect on electrophysiological properties of the hippocampal neurons by reversing the impaired synaptic efficacy caused by the CMS procedure and that the antidepressant effect of rTMS might be mediated by its protective action on the synaptic plasticity.

keywords
repetitive transcranial magnetic stimulation (rTMS), depression, chronic mild stress (CMS), long-term, 경두개자기자극(rTMS), 우울증, 만성스트레스(CMS), 장기상승작용(LTP), 전기경련충격(ECS)

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한국심리학회지: 인지 및 생물