title: Amyloid precursor protein maintains constitutive and adaptive plasticity of dendritic spines in adult brain by regulating D-serine homeostasis.
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.
authors: Department for Translational Brain Research, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.|Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany.
authors: Chengyu
authors: C
authors: Zou
authors: Department for Translational Brain Research, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.|Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany.|Munich Cluster of Systems Neurology (SyNergy), Ludwig-Maximilians-University, Munich, Germany.
authors: Sophie
authors: S
authors: Crux
authors: INSERM U1028, CNRS UMR5292, Lyon Neuroscience Research Center, team TIGER and AniRA Neurochem Technological platform, Lyon, France.
authors: Stephane
authors: S
authors: Marinesco
authors: Department for Translational Brain Research, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.|Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany.
authors: Elena
authors: E
authors: Montagna
authors: Department for Translational Brain Research, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
authors: Carmelo
authors: C
authors: Sgobio
authors: Department for Translational Brain Research, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.|Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany.
authors: Yuan
authors: Y
authors: Shi
authors: Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany.
authors: Song
authors: S
authors: Shi
authors: Department for Translational Brain Research, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.|Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany.
authors: Kaichuan
authors: K
authors: Zhu
authors: Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany.
authors: Mario M
authors: MM
authors: Dorostkar
authors: Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.
authors: Ulrike C
authors: UC
authors: Müller
authors: Department for Translational Brain Research, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany jochen.herms@med.uni-muenchen.de.|Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany.|Munich Cluster of Systems Neurology (SyNergy), Ludwig-Maximilians-University, Munich, Germany.
authors: Jochen
authors: 0000-0002-6201-1042
authors: J
authors: Herms
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003072:Cognition Disorders / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism*; D005260:Female; D006706:Homeostasis; D018345:Mice, Knockout; D009473:Neuronal Plasticity; D012694:Serine / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D012694:Serine
keywords: D‐serine; amyloid precursor protein; dendritic spine; microelectrode biosensor; spine plasticity; two‐photon in vivo imaging