Role of epidermal growth factor receptor signaling on dopamine D2 receptor-mediated dopamine neuron development
- 주제(키워드) Dopamine D2 receptor , Epidermal growth factor receptor , ERK , Mesencephalic dopaminergic neuron , Dopaminergic neuron development
- 발행기관 고려대학교 대학원
- 지도교수 백자현
- 발행년도 2016
- 학위수여년월 2016. 8
- 학위구분 석사
- 학과 대학원 생명과학과
- 세부전공 세포생물학
- 원문페이지 53 p
- 실제URI http://www.dcollection.net/handler/korea/000000069489
- 본문언어 영어
- 제출원본 000045881545
초록/요약
Dopamine D2 receptor (D2R) belongs to G protein-coupled receptors and plays a crucial role in neurophysiological functions of the dopaminergic system. It has been demonstrated that D2R regulates mesencephalic dopaminergic neuron development through epidermal growth factor receptor (EGFR) transactivation, leading to extracellular signal-regulated kinase (ERK) activation. In order to further investigate the role of EGFR on D2R-mediated dopaminergic neuron development, I generated conditional knockout mice of EGFR on their D2R-expressing cells by breeding Egfrf/f and D2R-Cre mice (Egfrf/f::D2R-Cre mice). Treatment with quinpirole, a D2R agonist, on the mesencephalic neurons from Egfrf/f mice induced ERK activation, but not in Egfrf/f::D2R-Cre mice. However, treatment with EGF or HB-EGF induced ERK activation both mice group. The number of basal mesencephalic dopaminergic neurons of Egfrf/f::D2R-Cre mice was lower than Egfrf/f mice and that treatment of quinpirole, EGF or HB-EGF increased the number of dopaminergic neurons in mesencephalic cultures from Egfrf/f mice but not in Egfrf/f::D2R-Cre mice. These findings suggest that EGFR has an important role in dopaminergic neuron development via D2R-EGFR-ERK pathway.
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List of Tables ………………………………………………ⅰ
List of Figures ………………………………………………ⅱ
Abstract ……………………………………………………ⅲ
Introduction ………………………………………………… 1
Material and Methods …………………………………… 4
1. Animal preparation and mesencephalic neuronal cell culture
2. Western Blot Analysis of p-ERK and p-EGFR
3. Immunocytochemistry
4. Immunohistochemistry and Immunofluorescence histochemistry
5. Behavioral analysis
- Animal
- Open field test
- Elevated plus maze test
- Cued fear conditioning
- Five-choice serial reaction time task (5-CSRTT)
- Measurement of Palatable food intake
- Cocaine sensitization
- Pre-pulse inhibition test
6. Statistical analysis
Results …………………………………………………… 11
1. Generation of Egfrf/f and Egfrf/f::D2R-Cre mice.
2. D2R-mediated ERK activation via EGFR phosphorylation in mesencephalic neuronal cells.
3. Role of EGFR in D2R-mediated dopaminergic neuron development.
4. Reduced TH expression in Egfrf/f::D2R-Cre mice.
5. Behavioral and physiological analysis of Egfrf/f::D2R-Cre mice.
Discussion ………………………………………………… 35
References ………………………………………………… 37
Abstract in Korean ……………………………………… 45
