title: Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer's disease.
abstract: Alterations of the dopaminergic (DAergic) system are frequently reported in Alzheimer's disease (AD) patients and are commonly linked to cognitive and non-cognitive symptoms. However, the cause of DAergic system dysfunction in AD remains to be elucidated. We investigated alterations of the midbrain DAergic system in the Tg2576 mouse model of AD, overexpressing a mutated human amyloid precursor protein (APPswe). Here, we found an age-dependent DAergic neuron loss in the ventral tegmental area (VTA) at pre-plaque stages, although substantia nigra pars compacta (SNpc) DAergic neurons were intact. The selective VTA DAergic neuron degeneration results in lower DA outflow in the hippocampus and nucleus accumbens (NAc) shell. The progression of DAergic cell death correlates with impairments in CA1 synaptic plasticity, memory performance and food reward processing. We conclude that in this mouse model of AD, degeneration of VTA DAergic neurons at pre-plaque stages contributes to memory deficits and dysfunction of reward processing.
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.|Unit of Molecular Neurosciences, Department of Medicine, University Campus-Biomedico, 00128 Rome, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Nobili
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.
authors.forename: Emanuele Claudio
authors.initials: EC
authors.lastname: Latagliata
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Viscomi
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.|Unit of Molecular Neurosciences, Department of Medicine, University Campus-Biomedico, 00128 Rome, Italy.
authors.forename: Virve
authors.initials: V
authors.lastname: Cavallucci
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Cutuli
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.|Institute of Cell Biology and Neurobiology (IBCN), National Research Council (CNR), 00143 Rome, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Giacovazzo
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.|Department of Systems Medicine, University of Rome 'Tor Vergata', 00133 Rome, Italy.
authors.forename: Paraskevi
authors.identifier: 0000-0002-8476-9233
authors.initials: P
authors.lastname: Krashia
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.|Department of Systems Medicine, University of Rome 'Tor Vergata', 00133 Rome, Italy.
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Rizzo
authors.affiliation: Unit of Molecular Neurosciences, Department of Medicine, University Campus-Biomedico, 00128 Rome, Italy.|Laboratory of Developmental Neuroscience and Neural Plasticity, Department of Medicine, University Campus-Biomedico, 00128 Rome, Italy.
authors.forename: Ramona
authors.initials: R
authors.lastname: Marino
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.
authors.forename: Mauro
authors.identifier: 0000-0003-4563-1677
authors.initials: M
authors.lastname: Federici
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.|Department of Technologies, Communication and Society (TECOS), University Guglielmo Marconi, 00193 Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: De Bartolo
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.|Department of Systems Medicine, University of Rome 'Tor Vergata', 00133 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Aversa
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.|Unit of Molecular Neurosciences, Department of Medicine, University Campus-Biomedico, 00128 Rome, Italy.
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Dell'Acqua
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.|Department of Systems Medicine, University of Rome 'Tor Vergata', 00133 Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Cordella
authors.affiliation: Department of Psychology, University Sapienza, 00185 Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sancandi
authors.affiliation: Laboratory of Developmental Neuroscience and Neural Plasticity, Department of Medicine, University Campus-Biomedico, 00128 Rome, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Keller
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.|Department of Psychology, University Sapienza, 00185 Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Petrosini
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.|Department of Psychology, University Sapienza, 00185 Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Puglisi-Allegra
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.|Department of Systems Medicine, University of Rome 'Tor Vergata', 00133 Rome, Italy.
authors.forename: Nicola Biagio
authors.initials: NB
authors.lastname: Mercuri
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.|Institute of Cell Biology and Neurobiology (IBCN), National Research Council (CNR), 00143 Rome, Italy.
authors.forename: Roberto
authors.identifier: 0000-0001-7059-7015
authors.initials: R
authors.lastname: Coccurello
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Berretta
authors.affiliation: Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.|Unit of Molecular Neurosciences, Department of Medicine, University Campus-Biomedico, 00128 Rome, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: D'Amelio
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D049229:Dendritic Spines / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005502:Food; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000150:complications / Q000473:pathology; D008568:Memory; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D009473:Neuronal Plasticity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000473:pathology / Q000503:physiopathology; D058225:Plaque, Amyloid / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D012201:Reward; D012642:Selegiline / Q000494:pharmacology / Q000627:therapeutic use; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
chemical_list: D012642:Selegiline; D004295:Dihydroxyphenylalanine