TY - JOUR
T1 - Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer's disease.
AU - Nobili, Annalisa
AU - Latagliata, Emanuele Claudio
AU - Viscomi, Maria Teresa
AU - Cavallucci, Virve
AU - Cutuli, Debora
AU - Giacovazzo, Giacomo
AU - Krashia, Paraskevi
AU - Rizzo, Francesca Romana
AU - Marino, Ramona
AU - Federici, Mauro
AU - De Bartolo, Paola
AU - Aversa, Daniela
AU - Dell'Acqua, Maria Concetta
AU - Cordella, Alberto
AU - Sancandi, Marco
AU - Keller, Flavio
AU - Petrosini, Laura
AU - Puglisi-Allegra, Stefano
AU - Mercuri, Nicola Biagio
AU - Coccurello, Roberto
AU - Berretta, Nicola
AU - D'Amelio, Marcello
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - neuronal loss
KW - neuronal loss
UR - http://hdl.handle.net/10807/132113
U2 - 10.1038/ncomms14727
DO - 10.1038/ncomms14727
M3 - Article
SN - 2041-1723
SP - N/A-N/A/A/A/A
JO - Nature Communications
JF - Nature Communications
ER -
