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Graduate School of Ajou University
Department of Neuroscience and Technology Course
3. Theses(Master)
염증 반응에 의한 도파민성 신경세포의 사멸과 Interleukin-4의 역할에 관한 연구
- Alternative Title
- Chung Eun Sook
- Author(s)
- 정은숙
- Alternative Author(s)
- Chung Eun Sook
- Advisor
- 진병관
- Department
- 일반대학원 신경과학기술과정
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2006-08
- Language
- eng
- Keyword
- Interleukin 4; Inflammation; microglia; leukocyte; dopaminergic neuron
- Alternative Abstract
- The present study showed that interleukin-4 was expressed in infiltrated T lymphocytes, and participated in the LPS-induced inflammatory processing and degeneration of dopaminergic neurons in the SN. In LPS-injected tissues, OX42-ip resident microglia (with ramified morphology) had activated morphology with large cell bodies and short processes, resulting in the expression of pro-inflammatory and/or cytotoxic factors, such as TNF-a IL-1b and iNOS. Previous studies determined that microglia undergo dramatic morphological changes from resting ramified cells to activated amoeboid microlgia. However, in the present study, it was thought that activated microglia (larger bodies and thicker processes) were died, but not changed amoeboid morphology, and amoeboid monocyte/macrophages were infiltrated into the SN, as expressing IL-1b and other inflammatory molecules. These infiltrated macrophages maybe participate to degeneration of dopaminergic neurons in the SN. Degeneration of TH-ip dopaminergic neurons paralleled with increasing of infiltration of macrophages, TH-ip dopaminergic neurons were started to die at 24 hr with damaged morphologies, such as small and shrunken cell bodies and short and dotted processes. And then most of TH-ip cells were disappeared from the SNpc, remaining some dotted processes at 3days and 7 days after intranigral injection of LPS. This neurotoxicity against dopaminergic neurons occurred in a time-dependent manner as determined by TH-ip cell counting. When quantified and expressed as a percentage of control values, treatment of LPS attenuated the number of TH-ip neurons by 26 - 72 % at 1 – 7 days, respectively compared with PBS treated control tissues. Neutralization of IL-4 effectively reduced LPS-induced degeneration of dopaminergic neurons, when quantified and expressed as the percentage of TH-ip neurons by 80 % compared with PBS-injected SN tissues. And also, in the LPS-injected tissue, OX42-ip cells were mostly presented as rounded morphology in the SN at 24hr, even at 1wk later. However, neutralization of IL-4 effectively reduced infiltration of rounded OX42-ip cells at 24hr, and only a few rounded OX42-ip cells were detected in the injected site at 1wk later. And also, neutralization of IL-4 effectively reduced ED1-ip phagocytes compared with LPS-injected tissues. When quantified and expressed as the percentage of ED1-ip cells on the ipsilateral SN, neutralization of IL-4 was found to reduce the number of ED1-ip cells in both SNpc and SNr by 43 % and 35 %, respectively, compared with LPS-injected SN tissues. Neutralization of IL-4 prevented the LPS-induced death of astrocytes and BBB disruption in the SN. These results suggest that interleukin-4 play important role in the LPS-mediated inflammatory process and degeneration of dopaminergic neurons by regulation of macrophage infiltration into the SN.
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- Graduate School of Ajou University > Department of Neuroscience and Technology Course > 3. Theses(Master)
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