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

Attilio Iemolo, Maria De Risi, Nadia Giordano, Giulia Torromino, Cristina Somma, Diletta Cavezza, Martina Colucci, Maria Mancini, Antonio De Iure, Rocco Granata, Barbara Picconi, Paolo Calabresi, Elvira De Leonibus

Research output: Contribution to journalArticle

Abstract

Cognitive deficits, including working memory, and visuospatial deficits are common and debilitating in Parkinson's disease. alpha-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 alpha-synucleinopathy. Here, we tested the hypothesis that pathologic alpha-Synuclein (alpha-Syn), initiated in different brain regions, leads to distinct onset and progression of the pathology. We report that overexpression of human alpha-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 alpha-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 alpha-synucleinopathy and provide functional evidence of the major neuronal networks involved in disease progression.
Original languageEnglish
Pages (from-to)N/A-N/A
Journalnpj Parkinson's Disease
Volume9
DOIs
Publication statusPublished - 2023

Keywords

  • Cognitive deficits
  • Parkinson's disease
  • Synaptic

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