Dopamine D2 receptor-mediated epidermal growth factor receptor signaling regulates neurogenesis in the subventricular zone of adult brain
Mechanisms underlying selective dopaminergic neuronal degeneration in Parkinson's disease (PD) remain unclear. Impaired adult neurogenesis has been implicated in PD pathology, but its molecular regulation is not fully understood. We previously reported that dopamine D2 receptor (D2R)-mediated e...
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Elsevier
2025-08-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125001950 |
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| author | Yea Jue Kim Byeong Jun Kang Jihee Seo Sion Kim Eun-chang Lee Ha-yeon Cho Donghoon Kim Im Joo Rhyu Ja-Hyun Baik |
| author_facet | Yea Jue Kim Byeong Jun Kang Jihee Seo Sion Kim Eun-chang Lee Ha-yeon Cho Donghoon Kim Im Joo Rhyu Ja-Hyun Baik |
| author_sort | Yea Jue Kim |
| collection | DOAJ |
| description | Mechanisms underlying selective dopaminergic neuronal degeneration in Parkinson's disease (PD) remain unclear. Impaired adult neurogenesis has been implicated in PD pathology, but its molecular regulation is not fully understood. We previously reported that dopamine D2 receptor (D2R)-mediated epidermal growth factor receptor (EGFR) signaling is critical for dopaminergic neuron development. To analyze how alterations in the dopamine system, especially D2R signaling in association with EGFR, contribute to dopamine-related dysfunction in vivo, we established a D2R cell-specific EGFR-deleted animal model, Drd2-Cre; EGFRf/f mice. These mice displayed a significant reduction in motor coordination ability and a decrease in the number of dopaminergic neurons in the midbrain, which resembles the characteristics of PD. We observed a reduction in the number of newly generated cells in the subventricular zone (SVZ) of aged Drd2-Cre; EGFRf/f mice, suggesting that the absence of EGFR in D2R-expressing cells could induce altered adult neurogenesis in the SVZ. Furthermore, when we compared the effect of l-3,4-dihydroxyphenylalanine (l-DOPA) on SVZ proliferation in 6-OHDA-lesioned control EGFRf/f and Drd2-Cre; EGFRf/f mice, the Drd2-Cre; EGFRf/f mice exhibited hindered L-DOPA-induced SVZ proliferation, indicating that D2R–EGFR signaling is necessary for the dopaminergic regulation of SVZ neurogenesis. These findings suggest that D2R–EGFR signaling is essential for maintaining midbrain dopaminergic neuron integrity and supporting adult neurogenesis, highlighting this pathway as a potential therapeutic target for promoting endogenous regenerative responses in PD. |
| format | Article |
| id | doaj-art-7bb566a943ee424ebd3fd7e12f3d67fe |
| institution | OA Journals |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-7bb566a943ee424ebd3fd7e12f3d67fe2025-08-20T02:02:47ZengElsevierNeurobiology of Disease1095-953X2025-08-0121210697910.1016/j.nbd.2025.106979Dopamine D2 receptor-mediated epidermal growth factor receptor signaling regulates neurogenesis in the subventricular zone of adult brainYea Jue Kim0Byeong Jun Kang1Jihee Seo2Sion Kim3Eun-chang Lee4Ha-yeon Cho5Donghoon Kim6Im Joo Rhyu7Ja-Hyun Baik8Department of Life Sciences, Korea University, Seoul 02841, Republic of KoreaDepartment of Life Sciences, Korea University, Seoul 02841, Republic of KoreaDepartment of Life Sciences, Korea University, Seoul 02841, Republic of KoreaDepartment of Life Sciences, Korea University, Seoul 02841, Republic of KoreaDepartment of Life Sciences, Korea University, Seoul 02841, Republic of KoreaDepartment of Life Sciences, Korea University, Seoul 02841, Republic of KoreaDepartment of Life Sciences, Korea University, Seoul 02841, Republic of KoreaDepartment of Anatomy, College of Medicine, Korea University, Seoul 02841, South KoreaDepartment of Life Sciences, Korea University, Seoul 02841, Republic of Korea; Corresponding author at: Molecular Neurobiology Laboratory, Department of Life Science, Korea University, Seoul 02841, South Korea.Mechanisms underlying selective dopaminergic neuronal degeneration in Parkinson's disease (PD) remain unclear. Impaired adult neurogenesis has been implicated in PD pathology, but its molecular regulation is not fully understood. We previously reported that dopamine D2 receptor (D2R)-mediated epidermal growth factor receptor (EGFR) signaling is critical for dopaminergic neuron development. To analyze how alterations in the dopamine system, especially D2R signaling in association with EGFR, contribute to dopamine-related dysfunction in vivo, we established a D2R cell-specific EGFR-deleted animal model, Drd2-Cre; EGFRf/f mice. These mice displayed a significant reduction in motor coordination ability and a decrease in the number of dopaminergic neurons in the midbrain, which resembles the characteristics of PD. We observed a reduction in the number of newly generated cells in the subventricular zone (SVZ) of aged Drd2-Cre; EGFRf/f mice, suggesting that the absence of EGFR in D2R-expressing cells could induce altered adult neurogenesis in the SVZ. Furthermore, when we compared the effect of l-3,4-dihydroxyphenylalanine (l-DOPA) on SVZ proliferation in 6-OHDA-lesioned control EGFRf/f and Drd2-Cre; EGFRf/f mice, the Drd2-Cre; EGFRf/f mice exhibited hindered L-DOPA-induced SVZ proliferation, indicating that D2R–EGFR signaling is necessary for the dopaminergic regulation of SVZ neurogenesis. These findings suggest that D2R–EGFR signaling is essential for maintaining midbrain dopaminergic neuron integrity and supporting adult neurogenesis, highlighting this pathway as a potential therapeutic target for promoting endogenous regenerative responses in PD.http://www.sciencedirect.com/science/article/pii/S0969996125001950Dopamine D2 receptorEpidermal growth factor receptorSubventricular zoneAdult neurogenesisParkinson's diseaseNeurodegenerative disorder |
| spellingShingle | Yea Jue Kim Byeong Jun Kang Jihee Seo Sion Kim Eun-chang Lee Ha-yeon Cho Donghoon Kim Im Joo Rhyu Ja-Hyun Baik Dopamine D2 receptor-mediated epidermal growth factor receptor signaling regulates neurogenesis in the subventricular zone of adult brain Neurobiology of Disease Dopamine D2 receptor Epidermal growth factor receptor Subventricular zone Adult neurogenesis Parkinson's disease Neurodegenerative disorder |
| title | Dopamine D2 receptor-mediated epidermal growth factor receptor signaling regulates neurogenesis in the subventricular zone of adult brain |
| title_full | Dopamine D2 receptor-mediated epidermal growth factor receptor signaling regulates neurogenesis in the subventricular zone of adult brain |
| title_fullStr | Dopamine D2 receptor-mediated epidermal growth factor receptor signaling regulates neurogenesis in the subventricular zone of adult brain |
| title_full_unstemmed | Dopamine D2 receptor-mediated epidermal growth factor receptor signaling regulates neurogenesis in the subventricular zone of adult brain |
| title_short | Dopamine D2 receptor-mediated epidermal growth factor receptor signaling regulates neurogenesis in the subventricular zone of adult brain |
| title_sort | dopamine d2 receptor mediated epidermal growth factor receptor signaling regulates neurogenesis in the subventricular zone of adult brain |
| topic | Dopamine D2 receptor Epidermal growth factor receptor Subventricular zone Adult neurogenesis Parkinson's disease Neurodegenerative disorder |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125001950 |
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