title: Reelin supplementation recovers synaptic plasticity and cognitive deficits in a mouse model for Angelman syndrome.
abstract: The Reelin signaling pathway is implicated in processes controlling synaptic plasticity and hippocampus-dependent learning and memory. A single direct in vivo application of Reelin enhances long-term potentiation, increases dendritic spine density and improves associative and spatial learning and memory. Angelman syndrome (AS) is a neurological disorder that presents with an overall defect in synaptic function, including decreased long-term potentiation, reduced dendritic spine density, and deficits in learning and memory, making it an attractive model in which to examine the ability of Reelin to recover synaptic function and cognitive deficits. In this study, we investigated the effects of Reelin administration on synaptic plasticity and cognitive function in a mouse model of AS and demonstrated that bilateral, intraventricular injections of Reelin recover synaptic function and corresponding hippocampus-dependent associative and spatial learning and memory. Additionally, we describe alteration of the Reelin profile in tissue from both the AS mouse and post-mortem human brain.
authors: USF Health Byrd Alzheimer's Institute, 4001 East Fletcher Avenue, Tampa, FL, 33613, USA.|Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA.
authors: Whitney R
authors: WR
authors: Hethorn
authors: USF Health Byrd Alzheimer's Institute, 4001 East Fletcher Avenue, Tampa, FL, 33613, USA.|Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA.
authors: Stephanie L
authors: SL
authors: Ciarlone
authors: USF Health Byrd Alzheimer's Institute, 4001 East Fletcher Avenue, Tampa, FL, 33613, USA.|Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA.
authors: Irina
authors: I
authors: Filonova
authors: USF Health Byrd Alzheimer's Institute, 4001 East Fletcher Avenue, Tampa, FL, 33613, USA.|Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA.
authors: Justin T
authors: JT
authors: Rogers
authors: Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA.
authors: Daniela
authors: D
authors: Aguirre
authors: USF Health Byrd Alzheimer's Institute, 4001 East Fletcher Avenue, Tampa, FL, 33613, USA.|Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA.
authors: Raquel A
authors: RA
authors: Ramirez
authors: USF Health Byrd Alzheimer's Institute, 4001 East Fletcher Avenue, Tampa, FL, 33613, USA.|Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA.
authors: Joseph C
authors: JC
authors: Grieco
authors: USF Health Byrd Alzheimer's Institute, 4001 East Fletcher Avenue, Tampa, FL, 33613, USA.|Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA.
authors: Melinda M
authors: MM
authors: Peters
authors: USF Health Byrd Alzheimer's Institute, 4001 East Fletcher Avenue, Tampa, FL, 33613, USA.|Department of Molecular Medicine, University of South Florida, Tampa, FL, USA.
authors: Danielle
authors: D
authors: Gulick
authors: Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors: Anne E
authors: AE
authors: Anderson
authors: USF Health Byrd Alzheimer's Institute, 4001 East Fletcher Avenue, Tampa, FL, 33613, USA.|Department of Molecular Medicine, University of South Florida, Tampa, FL, USA.
authors: Jessica
authors: J
authors: L Banko
authors: USF Health Byrd Alzheimer's Institute, 4001 East Fletcher Avenue, Tampa, FL, 33613, USA.|Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA.
authors: April L
authors: AL
authors: Lussier
authors: USF Health Byrd Alzheimer's Institute, 4001 East Fletcher Avenue, Tampa, FL, 33613, USA.|Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA.
authors: Edwin J
authors: EJ
authors: Weeber
mesh_terms: D017204:Angelman Syndrome / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology*; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000008:administration & dosage* / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000008:administration & dosage* / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D006801:Humans; D007276:Injections, Intraventricular; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000008:administration & dosage* / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000008:administration & dosage* / Q000378:metabolism; D065853:Spatial Learning / Q000187:drug effects; D065852:Spatial Memory / Q000187:drug effects
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases
keywords: behavior; cannulation; hippocampus; ubiquitin ligase; ventricle