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Synaptic mechanisms underlying onset and progression of memory deficits caused by hippocampal and midbrain synucleinopathy

Cognitive deficits, including working memory, and visuospatial deficits are common and debilitating in Parkinson’s disease. α-synucleinopathy in the hippocampus and cortex is considered as the major risk factor. However, little is known about the progression and specific synaptic mechanisms underlyi...

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Detalles Bibliográficos
Autores principales: Iemolo, Attilio, De Risi, Maria, Giordano, Nadia, Torromino, Giulia, Somma, Cristina, Cavezza, Diletta, Colucci, Martina, Mancini, Maria, de Iure, Antonio, Granata, Rocco, Picconi, Barbara, Calabresi, Paolo, De Leonibus, Elvira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10275870/
https://www.ncbi.nlm.nih.gov/pubmed/37328503
http://dx.doi.org/10.1038/s41531-023-00520-1
Descripción
Sumario:Cognitive deficits, including working memory, and visuospatial deficits are common and debilitating in Parkinson’s disease. α-synucleinopathy in the hippocampus and cortex is considered as the major risk factor. However, little is known about the progression and specific synaptic mechanisms underlying the memory deficits induced by α-synucleinopathy. Here, we tested the hypothesis that pathologic α-Synuclein (α-Syn), initiated in different brain regions, leads to distinct onset and progression of the pathology. We report that overexpression of human α-Syn in the murine mesencephalon leads to late onset memory impairment and sensorimotor deficits accompanied by reduced dopamine D1 expression in the hippocampus. In contrast, human α-Syn overexpression in the hippocampus leads to early memory impairment, altered synaptic transmission and plasticity, and decreased expression of GluA1 AMPA-type glutamate receptors. These findings identify the synaptic mechanisms leading to memory impairment induced by hippocampal α-synucleinopathy and provide functional evidence of the major neuronal networks involved in disease progression.