Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer’s disease

Annalisa Nobili, Emanuele Claudio Latagliata, Maria Teresa Viscomi, Virve Cavallucci, Debora Cutuli, Giacomo Giacovazzo, Paraskevi Krashia, Francesca Romana Rizzo, Ramona Marino, Mauro Federici, Paola De Bartolo, Daniela Aversa, Maria Concetta Dell’Acqua, Alberto Cordella, Marco Sancandi, Flavio Keller, Laura Petrosini, Stefano Puglisi-Allegra, Nicola Biagio Mercuri, Roberto Coccurello, Nicola Berretta and Marcello D’Amelio ()
Additional contact information
Annalisa Nobili: IRCCS Santa Lucia Foundation
Emanuele Claudio Latagliata: IRCCS Santa Lucia Foundation
Maria Teresa Viscomi: IRCCS Santa Lucia Foundation
Virve Cavallucci: IRCCS Santa Lucia Foundation
Debora Cutuli: IRCCS Santa Lucia Foundation
Giacomo Giacovazzo: IRCCS Santa Lucia Foundation
Paraskevi Krashia: IRCCS Santa Lucia Foundation
Francesca Romana Rizzo: IRCCS Santa Lucia Foundation
Ramona Marino: Unit of Molecular Neurosciences, University Campus-Biomedico
Mauro Federici: IRCCS Santa Lucia Foundation
Paola De Bartolo: IRCCS Santa Lucia Foundation
Daniela Aversa: IRCCS Santa Lucia Foundation
Maria Concetta Dell’Acqua: IRCCS Santa Lucia Foundation
Alberto Cordella: IRCCS Santa Lucia Foundation
Marco Sancandi: University Sapienza
Flavio Keller: Laboratory of Developmental Neuroscience and Neural Plasticity, University Campus-Biomedico
Laura Petrosini: IRCCS Santa Lucia Foundation
Stefano Puglisi-Allegra: IRCCS Santa Lucia Foundation
Nicola Biagio Mercuri: IRCCS Santa Lucia Foundation
Roberto Coccurello: IRCCS Santa Lucia Foundation
Nicola Berretta: IRCCS Santa Lucia Foundation
Marcello D’Amelio: IRCCS Santa Lucia Foundation

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14727

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