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.
Nobili, A., Latagliata, E., Viscomi, M. T., Cavallucci, V., Cutuli, D., Giacovazzo, G., Krashia, P., Rizzo, F., Marino, R., Federici, M., De Bartolo, P., Aversa, D., Dell'Acqua, M., Cordella, A., Sancandi, M., Keller, F., Petrosini, L., Puglisi-Allegra, S., Mercuri, N., Coccurello, R., Berretta, N., D'Amelio, M., Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer's disease., <<NATURE COMMUNICATIONS>>, 2017; (8:14727): N/A-N/A/A/A/A. [doi:10.1038/ncomms14727] [http://hdl.handle.net/10807/132113]
Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer's disease.
Viscomi, Maria TeresaMembro del Collaboration Group
;Cavallucci, V;
2017
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.
| File | Dimensione | Formato | |
|---|---|---|---|
|
Nobili et al., 2017 Nature Communications.pdf
accesso aperto
Tipologia file ?:
Versione Editoriale (PDF)
Licenza:
Creative commons
Dimensione
2.82 MB
Formato
Adobe PDF
|
2.82 MB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
