[보고서]활성미세아교세포는 손상된 신경세포의 사멸을 촉진하고, 주변 bystander neuron을 공격한다

송대용

활성미세아교세포는 손상된 신경세포의 사멸을 촉진하고, 주변 bystander neuron을 공격한다
Activated microglia could promote the damaged neuronal cell loss and could attack bystander neurons 원문보기

보고서 정보
주관연구기관	을지대학교 산학협력단
연구책임자	송대용
보고서유형	최종보고서
발행국가	대한민국
언어	한국어
발행년월	2011-06
과제시작연도	2010
주관부처	교육과학기술부
사업 관리 기관	한국연구재단
등록번호	TRKO201200002525
과제고유번호	1345119939
사업명	일반연구자지원
DB 구축일자	2013-05-20
키워드	내측전뇌다발.축삭절단.미세아교세포.도파민신경세포.medial forebrain bundle.axotomy.microglia.dopaminergic neuron.Tuftsin fragment 1-3.ROS.

초록

미세아교세포는 평상시에는 중추신경계의 면역감시자로서 기능하나 과도하게 활성화된 미세아교세포는 오히려 신경세포의 생존에 부정적인 역할을 미칠 수 있음이 몇몇 연구에 의해 증명된 바 있다. 이번 연구에서 연구자는 활성미세아교세포에서 과도하게 ROS가 생성, 분비되며, 이로 인해 손상된 신경세포의 사멸을 촉진하고, 심지어는 주변 정상 bystander neuron까지도 공격할 수 있음을 in vivo, ex vivo, invitro 연구를 통해 증명하고자 하였다.

Abstract ▼

Under physiological condition, microglia, the resident immune cell of the central nervous system (CNS), play an important role in maintenance and restoration of the brain by scavenging the invading infectious agents and removing the noxious materials or dying cells. However, there are also many opposite evidences that activated microglia could be involved in a number of pathogenesis in the CNS. In this study, the author will present some experimental evidences that activated microglia could have a deteriorative role in the survival of damaged neurons by producing excessive ROS and they also could attack neighboring bystander neurons.

목차 Contents

일반연구자지원사업 최종보고서 ... 1
목차 ... 3
I. 연구 계획 요약문 ... 4
1. 국문 요약문 ... 4
II. 연구 결과 요약문 ... 5
1. 국문 요약문 ... 5
2. 영문 요약문 ... 6
III. 연구내용 및 결과 ... 7
1. 연구개발과제의 개요 ... 7
2. 국내외 기술개발 현황 ... 10
3. 연구수행 내용 및 결과 ... 13
4. 목표 달성도 및 관련 분야에의 기여도 ... 49
5. 연구결과의 활용계획 ... 51
6. 연구과정에서 수집한 해외과학기술정보 ... 52
7. 주관연구책임자(공동연구원) 대표적 연구 실적 ... 52
8. 참고 문헌 ... 53
9. 연구 성과 ... 61
10. 기타사항(중요 연구 변경사항 등) ... 61

표/그림 (23)

표 가설. 특정 요인에 의해 활성화된 미세아교세포는 강하게 ROS를 내어 주변의 bystander neuron도 공격할 수 있다.
표 연구개발 내용.
표 Sagittal (A) and coronal (B) view of the adult rat brain illustrating how the medial forebrain bundle (MFB) transection is conducted.
표 The graphical illustration which demonstrate the MFB hemi-axotomy methodand Fluorogold(FG) injection into the striatum.
표 The illustrative demonstration how we can deliver the Tuftsin fragment 1-3 into the lateral ventricle using mini-osmotic pump.
표 Changes in the number of tyrosine hydroxylase-immunoreactive neurons of the substantia nigra following unilateral transection of the medial forebrain bundle. Single asterisk denotes P< 0.005, double asterisks P< 0.001.
표 High magnifications of TH and OX6 double labeling in the contralateral (A) and ipsilateral (B and C) SN at 14 dpl. OX6 positive (black) activated microglia specifically stick to TH immunoreactive nigrostriatal fibers (arrows in B), and soma (arrows in C). Scale bar represents 30 um.
표 Triple immunohistochemistry for TH (purple), ED1 (black) and OX6 (brown) at the level ofintermediate SN; (a-d), 7dpl; (e-h), 14 dpl. Higher magnifications (b-d and f-h) represent the areasmarked with squares in (a) and (e). Scale bars = 500 um in (a); 50 um in (h).
표 Representative ethidium fluorescence in SN of the contralateral (A) and ipsilateral side at 7dpl (B), 14 dpl (C), and 28 dpl (D).
표 (A)-(D) are photographs of double immunolabeling of OX6 (C and D) or ED1 (E and F) with FG in the contralateral (A and C) and ipsilateral SN (B and D) at 14 days post MFB hemi-axotomy and FG injection. Note that OX6 positive microglia and their phagocytic activities were superimposed on the soma (arrows) and processes (arrowheads) of the FG-ir unaxotomied intact neurons.(E) and (F) are immuno-EM result demonstrating that activated microglia are closely attached to the FG-positive bystander neuron. Scale bar = 50 ㎛.
표 Double immunolabeling of activated microglia (OX6) and DA neurons (TH) in the contralateral (A) and ipsilateral SN (B and C) at 14 days post lesion. In vehicle treated animals, innumerable OX6 positive microglia are crowed in the ipsilateral SN (B). However, in Tuftsin fragment 1-3 treated animal, the OX6 immunoreactivies are deeply suppressed. There areno notable microglial activities in the contralateral SN in both vehicle and Tuftsin fragment 1-3treated animals (A). (D) and (E) is representative photographs showing theTH-immunoreactivities in the ipsilateral SN in vehicle and Tuftsin fragment 1-3 treated animals at 14 days post lesion, respectively. (F) is the diagram showing the relative survival percentage of nigral TH-immunoreactive neurons. Scale bar = 250 ㎛.
표 OptiPrep gradient separation according to the gradient difference.
$OptiPrep gradient separation of substantia nigra celluar pool from the brains of 6-month-old Wistar rat. Note that we can identify microglia pellet in the bottom of the 15-ml bottle. The right figures show the cellular coponents in each fraction.$ 표 OptiPrep gradient separation of substantia nigra celluar pool from the brains of 6-month-old Wistar rat. Note that we can identify microglia pellet in the bottom of the 15-ml bottle. The right figures show the cellular coponents in each fraction.
표 Immunocytochemistry of OX42, OX6, GFAP, and NeuN against primary cultured microglia.
표 Diagram showing the relative OX42-, OX6-, NeuN-, and GFAP-immunoreactive cells in primary cultured Fraction4.
표 LPS treatment increased intracellular ROS production in primary cultured microglia. Microglia were treated with 100 ul HBSS containing different concentrations of LPS for 1h and then with 20 uM DCFH-DA in 100 ul HBSS for 1h. After 2h, fluorescence was read immediately at 485 nm for exciation and 530 nm for emission with a fluorescence plate reader.
표 Microglia were pretreated for 30 min with different concentration of Tuftsin fragment 1-3 followed by the addition of LPS (1 ng/ml). The ROS production was measured by DCFH-DA method.
표 - 42 - Immunocytochemistry of OX6 and NOS against primary cultured microglia which are cultivated from MFB axotomized SN after 10 days post lesion. Abundant of microglia expressed MHC class II andNOS, which means that they are highly activated. Scale bar represents 20 um.
표 (A) Photograph of haetoxyline injection into the substantianigra (SN) and (B) the schematic diagram.
표 (A) TH immunohistochemistry in the ipsilateral substantia nigra at 14 days after vehicle (Sham) or activated microglia (MG) implantation. Scale bar represent 300 um. (B) Changes in the number of TH immunoreactive neurons in the ipsilateral vehicle or activated microglia implanted SN compared with contralateral SN.
표 Pair-wise scatter plots with control (n=2), 1 day post-lesion (n=2), 3 day post-lesion (n=2), 7 day post-lesion (n=3), and 14 day post-lesion (n=3).
표 The number of probes witch is up-regulated (red bar) or down-regulated (green) probes compared with the control groups.
표 Double immunofluorescence of OX6 and Hsp27 and their merged image. Scal bar represents 30 um.

과제명(ProjectTitle) :	-
연구책임자(Manager) :	-
과제기간(DetailSeriesProject) :	-
총연구비 (DetailSeriesProject) :	-
키워드(keyword) :	-
과제수행기간(LeadAgency) :	-
연구목표(Goal) :	-
연구내용(Abstract) :	-
기대효과(Effect) :	-

내보내기 구분	파일저장 인쇄 메일전송
구성항목	기본정보 상세정보 관리번호, 제목(한글), 저자명(한글), 발행일자, 전자원문, 초록(한글), 초록(영문) 관리번호, 제목(한글), 제목(영문), 저자명(한글), 저자명(영문), 주관연구기관(한글), 주관연구기관(영문), 발행일자, 총페이지수, 주관부처명, 과제시작일, 보고서번호, 과제종료일, 주제분류, 키워드(한글), 전자원문, 키워드(영문), 입수제어번호, 초록(한글), 초록(영문), 목차
저장형식	Text(ASCII format) Excel format
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

연합인증

활성미세아교세포는 손상된 신경세포의 사멸을 촉진하고, 주변 bystander neuron을 공격한다
Activated microglia could promote the damaged neuronal cell loss and could attack bystander neurons 원문보기