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학술저널
저자정보
이현주 (대구경북과학기술원부설한국뇌연구원) 박진희 (대구경북과학기술원부설한국뇌연구원) Justin H. Trotter (USF Health Byrd Alzheimer’s Institute University of South Florida) James N. Maher (Department of Neuroscience Georgetown University Medical Center) Kathleen E. Keenoy (Department of Neuroscience Georgetown University Medical Center) 장유미 (한국뇌연구원) 이영은 (울산과학기술원) 김재익 (울산과학기술원) Edwin J. Weeber (Department of Molecular Pharmacology and Physiology USF Health Byrd Alzheimer’s Institute) 허향숙 (대구경북과학기술원부설한국뇌연구원)
저널정보
한국뇌신경과학회 Experimental Neurobiology Experimental Neurobiology Vol.32 No.1
발행연도
2023.2
수록면
42 - 55 (14page)

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Amyloid precursor protein (APP) plays an important role in the pathogenesis of Alzheimer’s disease (AD), but the normal function of APP at syn- apses is poorly understood. We and others have found that APP interacts with Reelin and that each protein is individually important for dendritic spine formation, which is associated with learning and memory, in vitro . However, whether Reelin acts through APP to modulate dendritic spine formation or synaptic function remains unknown. In the present study, we found that Reelin treatment significantly increased dendritic spine density and PSD-95 puncta number in primary hippocampal neurons. An examination of the molecular mechanisms by which Reelin regulates dendritic spinogenesis revealed that Reelin enhanced hippocampal dendritic spine formation in a Ras/ERK/CREB signaling-dependent manner. Interestingly, Reelin did not increase dendritic spine number in primary hippocampal neurons when APP expression was reduced or in vivo in APP knockout (KO) mice. Taken together, our data are the first to demonstrate that Reelin acts cooperatively with APP to modulate dendritic spine formation and suggest that normal APP function is critical for Reelin-mediated dendritic spinogenesis at synapses.

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