298 420

Cited 0 times in

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 
Issue Date
Dept. of Medicine/박사
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.
Files in This Item:
T014354.pdf Download
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
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.