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Effect of hypothyroidism on 5-HT1A receptors in the rat brain measured by [18F]Mefway PET

Other Titles
 18F]Mefway 양전자방출단층촬영술로 측정한 갑상선기능저하증이 쥐 뇌의 세로토닌 1A 수용체에 미치는 영향 
Authors
 이재훈 
Issue Date
2017
Description
Dept. of Medicine/박사
Abstract
This study investigated the effects of hypothyroidism on the brain serotonin (5-HT) 1A receptor using animal disease models and 4-(trans-[18F]fluoranylmethyl)-N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexane-1-carboxamide ([18F]Mefway) positron emission tomography (PET) imaging.
Five surgically thyroidectomized male Sprague-Dawley rats were assigned to the hypothyroidism group, and five sham-operated male Sprague-Dawley rats were assigned to the control group. Hypothyroid status was confirmed by thyroid function tests. After anesthesia with 2.0% isoflurane in oxygen, fluconazole was infused at a constant rate for one hour to prevent defluorination of the radioligand. Then [18F]Mefway of 8.6–11.1 MBq was administered at a rate of 1 ml/min and dynamic PET scans were performed over the course of 120 min. PET data were reconstructed in user-defined time frames using a two-dimensional ordered-subset expectation maximization algorithm.
All PET data were spatially normalized to T2-weighted magnetic resonance imaging templates, and then time-activity curves of the hippocampus, septum, and cerebellum were extracted using predefined volume of interest templates. Non-displaceable binding values in the hippocampus and septum were calculated using a multilinear reference tissue model, with the cerebellum as the reference tissue, and a ligand-specific parametric map was constructed.
Time-activity curves revealed that the hippocampal and septal uptakes in the hypothyroidism group were 25–52% higher than those in the control group, and non-displaceable binding potentials in the same regions of thyroidectomized rat brains were about 30% higher than those in controls.
In conclusion, hypothyroidism increased the density of postsynaptic 5-HT1A receptors in the hippocampus and septum. Upregulation of postsynaptic 5-HT1A receptors may be responsible for the increased radioligand uptake as an early response to the reduced synaptic concentration of 5-HT caused by hypothyroidism.


이 연구는 동물 질병 모델 및 4-(trans-[18F]fluoranylmethyl)-N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexane-1-carboxamide ([18F]Mefway) 양전자방출단층촬영술(PET)을 사용하여 갑상선기능저하증이 뇌의 세로토닌 1A 수용체에 미치는 영향을 연구하였다.
갑상선절제술을 받은 Sprague-Dawley 수컷 쥐 5마리를 갑상선기능저하증 집단에 배정하였고, 모의 수술(sham operation)을 받은 Sprague-Dawley 수컷 쥐 5마리를 대조군으로 설정하였다. 갑상선기능저하 상태는 갑상선 기능 검사로 확인하였다. 산소에 2%의 아이소플루레인을 혼합하여 마취를 시킨 후, [18F]Mefway의 탈불소화를 방지하기 위하여, 1시간 동안 플루코나졸을 투여하였다. 그 다음 8.6–11.1 MBq의 [18F]Mefway를 1 ml/min 속도로 투여한 후, PET 영상을 120분간 연속적으로 획득하였다. PET 영상은 2차원 정칙화된 기댓값 최대화 알고리즘(ordered subsets expectation maximization algorithm)을 이용하여 재구성하였다.
모든 PET 영상은 T2 강조 자기공명영상 틀(template)에 공간정규화 한 후 사전 정의된 관심영역 틀을 이용하여 해마, 사이막(septum), 소뇌의 시간방사능곡선을 추출하였다. 해마와 사이막의 수용체 결합능(non-displaceable binding potential)은 소뇌를 참조조직으로 삼아 다중선형 참조조직 모형(multilinear reference tissue model)을 통하여 계산하였고 리간드-특정 모수지도(parametric map)를 작성하였다.
시간방사능곡선에서 갑상선기능저하증 집단의 해마와 사이막 섭취는 대조군보다 25-52% 더 많았고 이 부위의 결합능은 갑상선절제술을 받은 쥐에서 대조군에 비하여 30% 가량 더 높았다.
결론적으로, 갑상선기능저하증은 해마와 사이막의 시냅스후 세로토닌 1A 수용체 밀도를 증가시켰다. 이는 갑상선기능저하증으로 인해 시냅스의 세로토닌 농도가 감소하고 이에 따른 초기 반응으로써 시냅스후 세로토닌 1A 수용체가 상향조절 되었기 때문일 것이다.
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 3. Dissertation
Yonsei Authors
Lee, Jae Hoon(이재훈) ORCID logo https://orcid.org/0000-0002-9898-9886
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154891
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