• 한국발생생물학회:학술대회논문집
• /
• 한국발생생물학회 2003년도 제3회 국제심포지움 및 학술대회
• /
• pp.103-103
• /
• 2003

The purpose of this study is to evaluate an efficacy of in vitro differentiated human embryonic stem (hES, MB03) cells expressing Nurr1 in relief of symptomatic motor behavior of Parkinson's disease (PD) animal models MB03 was genetically modified to express Nurr1 protein and was induced to differentiate according to 2-/4+ protocol using retinoic acid and ascorbic acid. The differentiation-induced cells were selected for 10 to 20 days thereafter in N2 medium. Upon selection, cells expressing GFAP, TH, or NF200 were 38.8%, 11%, and 20.5%, respectively. in order to examine therapeutic effects of the differentiated cells in PD animal model, rats were unilaterally lesioned by administration of 6-kydroxydopamine HCI (6-OHDA) into medial forebrain region (MFB, AP -4.4 mm, ML 1.2 mm, DV 78 mm with incision bar set at -2.4 mm), as a reference to bregma and the surface of the skull. Confirmation of successful lesion by apomorphine-induced rotational behavior, differentiated cells were transplanted into the striatum (AP 1.0, ML 3.5, DV -5.0; AP 0.6, ML 2.5, DV -4.5). Improvements of asymmetric motor behavior by the transplantation were examined every two weeks after the surgery. In two weeks, numbers of rotation by the experimental rats were $-14.8 \pm 33.9%$ (P<0.05) of the number before transplantation, however, the ratio increased slightly to $13.6 \pm 56.3%$ in six weeks. In contrast, the ratio of sham-grafted animals ranged from 112.3+8.5% to 139.2+28.9% during the examination. Immunohistochemical studies further confirmed the presence, survival, migration, and expression of TH of the transplanted human cells.

• Biomolecules & Therapeutics
• /
• 제31권3호
• /
• pp.264-275
• /
• 2023

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by tremors, bradykinesia, and rigidity. PD is caused by loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN) and therefore, replenishment of DA neurons via stem cell-based therapy is a potential treatment option. Astrocytes are the most abundant non-neuronal cells in the central nervous system and are promising candidates for reprogramming into neuronal cells because they share a common origin with neurons. The ability of neural progenitor cells (NPCs) to proliferate and differentiate may overcome the limitations of the reduced viability and function of transplanted cells after cell replacement therapy. Achaete-scute complex homolog-like 1 (Ascl1) is a well-known neuronal-specific factor that induces various cell types such as human and mouse astrocytes and fibroblasts to differentiate into neurons. Nurr1 is involved in the differentiation and maintenance of DA neurons, and decreased Nurr1 expression is known to be a major risk factor for PD. Previous studies have shown that direct conversion of astrocytes into DA neurons and NPCs can be induced by overexpression of Ascl1 and Nurr1 and additional transcription factors genes such as superoxide dismutase 1 and SRY-box 2. Here, we demonstrate that astrocytes isolated from the ventral midbrain, the origin of SN DA neurons, can be effectively converted into DA neurons and NPCs with enhanced viability. In addition, when these NPCs are inducted to differentiate, they exhibit key characteristics of DA neurons. Thus, direct conversion of midbrain astrocytes is a possible cell therapy strategy to treat neurodegenerative diseases.

• 한국수정란이식학회:학술대회논문집
• /
• 한국수정란이식학회 2003년도 제3회 발생공학 국제심포지움 및 학술대회
• /
• pp.103-103
• /
• 2003

• 한국수정란이식학회:학술대회논문집
• /
• 한국수정란이식학회 2003년도 제3회 발생공학 국제심포지움 및 학술대회
• /
• pp.104-104
• /
• 2003

• 대한생식의학회:학술대회논문집
• /
• 대한불임학회 2002년도 제42차 춘계학술대회
• /
• pp.90-90
• /
• 2002

• 한국동물학회:학술대회논문집
• /
• 한국동물학회 2001년도 한국생물과학협회 학술발표대회
• /
• pp.214.2-215
• /
• 2001

No Abstract, See Full Text

• 대한생식의학회:학술대회논문집
• /
• 대한불임학회 2003년도 제45차 추계학술대회
• /
• pp.157-157
• /
• 2003

• 대한생식의학회:학술대회논문집
• /
• 대한불임학회 2003년도 제45차 추계학술대회
• /
• pp.156.2-157
• /
• 2003

• 자원환경지질
• /
• 제48권4호
• /
• pp.313-324
• /
• 2015

본 연구는 몽골 아르항가이 주 남동부 지역에 위치하는 우기누르 철-망간 광화대에 대해 3차원 지질모델을 구축하고 자력탐사와 비교 분석하여 지질 내 광체의 분포 특성을 유추하였다. 단면도 구축, Surface 모델링, 엽리 모델링 및 솔리드 모델링의 4단계로 3차원 지질모델을 구축한 결과, 연구지역 1과 2는 북서방향의 단층을 경계로 서부에는 문군체층이 동부에는 야실층이 분포하며 지질암체 내 표현된 엽리의 주된 주향 방향은 북서방향을 보이며 이러한 경향성은 지질경계를 이루는 북서방향 단층과의 유사하다. 연구지역의 자력탐사 자료를 이상치 분포특성에 따라 살펴본 결과, 자화율의 임계값이 낮을수록 이상치 분포대가 수직적인 분포를 보이는 경향이 관찰되나 임계값이 높아짐에 따라 이상대의 분포가 점차 지표 및 이와 인접한 천부에 집중된다. 자력탐사 이상대의 분포와 지질분포를 3차원 상에서 비교분석한 결과, 연구지역 1에서 자력탐사 이상대의 분포가 주로 북서방향 단층의 서부에 분포하는 문군체층에 신장된 형태의 렌즈상으로 분포하나, 연구지역 2의 경우 문군체층과 야실층에 균등한 분포를 보인다. 3차원 지질모델과 자력탐사 분포 특성을 비교분석 결과를 살펴보았을 때 본 연구지역에서는 실루리아기에 광화작용과 연관된 화산활동이 있었으며, 이 후 발생한 구조운동에 의해 광화대가 구조선을 따라 재배열 된 것으로 생각된다.

• Molecules and Cells
• /
• 제41권8호
• /
• pp.742-752
• /
• 2018

Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive degeneration of dopaminergic (DAergic) neurons, particularly in the substantia nigra (SN). Although circadian dysfunction has been suggested as one of the pathophysiological risk factors for PD, the exact molecular link between the circadian clock and PD remains largely unclear. We have recently demonstrated that $REV-ERB{\alpha}$, a circadian nuclear receptor, serves as a key molecular link between the circadian and DAergic systems. It competitively cooperates with NURR1, another nuclear receptor required for the optimal development and function of DA neurons, to control DAergic gene transcription. Considering our previous findings, we hypothesize that $REV-ERB{\alpha}$ may have a role in the onset and/or progression of PD. In the present study, we therefore aimed to elucidate whether genetic abrogation of $REV-ERB{\alpha}$ affects PD-related phenotypes in a mouse model of PD produced by a unilateral injection of 6-hydroxydopamine (6-OHDA) into the dorsal striatum. $REV-ERB{\alpha}$ deficiency significantly exacerbated 6-OHDA-induced motor deficits as well as DAergic neuronal loss in the vertebral midbrain including the SN and the ventral tegmental area. The exacerbated DAergic degeneration likely involves neuroinflammation-mediated neurotoxicity. The $REV-erb{\alpha}$ knockout mice showed prolonged microglial activation in the SN along with the over-production of interleukin $1{\beta}$, a pro-inflammatory cytokine, in response to 6-OHDA. In conclusion, the present study demonstrates for the first time that genetic abrogation of $REV-ERB{\alpha}$ can increase vulnerability of DAergic neurons to neurotoxic insults, such as 6-OHDA, thereby implying that its normal function may be beneficial for maintaining DAergic neuron populations during PD progression.