Amyloid precursor protein maintains constitutive and adaptive plasticity of dendritic spines in adult brain by regulating D‐serine homeostasis |
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| Authors: | Chengyu Zou Sophie Crux Stephane Marinesco Elena Montagna Carmelo Sgobio Yuan Shi Song Shi Kaichuan Zhu Mario M Dorostkar Ulrike C Müller Jochen Herms |
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| Affiliation: | 1. Department for Translational Brain Research, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany;2. Center for Neuropathology and Prion Research, Ludwig–Maximilians‐University, Munich, Germany;3. Munich Cluster of Systems Neurology (SyNergy), Ludwig‐Maximilians‐University, Munich, Germany;4. INSERM U1028, CNRS UMR5292, Lyon Neuroscience Research Center, team TIGER and AniRA Neurochem Technological platform, Lyon, France;5. Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany |
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| Abstract: | Dynamic synapses facilitate activity‐dependent remodeling of neural circuits, thereby providing the structural substrate for adaptive behaviors. However, the mechanisms governing dynamic synapses in adult brain are still largely unknown. Here, we demonstrate that in the cortex of adult amyloid precursor protein knockout (APP‐KO) mice, spine formation and elimination were both reduced while overall spine density remained unaltered. When housed under environmental enrichment, APP‐KO mice failed to respond with an increase in spine density. Spine morphology was also altered in the absence of APP. The underlying mechanism of these spine abnormalities in APP‐KO mice was ascribed to an impairment in D‐serine homeostasis. Extracellular D‐serine concentration was significantly reduced in APP‐KO mice, coupled with an increase of total D‐serine. Strikingly, chronic treatment with exogenous D‐serine normalized D‐serine homeostasis and restored the deficits of spine dynamics, adaptive plasticity, and morphology in APP‐KO mice. The cognitive deficit observed in APP‐KO mice was also rescued by D‐serine treatment. These data suggest that APP regulates homeostasis of D‐serine, thereby maintaining the constitutive and adaptive plasticity of dendritic spines in adult brain. |
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| Keywords: | amyloid precursor protein dendritic spine D‐serine microelectrode biosensor spine plasticity two‐photon in vivo imaging |
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