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


ABSTRACT: 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.

SUBMITTER: Iemolo A 

PROVIDER: S-EPMC10275870 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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

Iemolo Attilio A   De Risi Maria M   Giordano Nadia N   Torromino Giulia G   Somma Cristina C   Cavezza Diletta D   Colucci Martina M   Mancini Maria M   de Iure Antonio A   Granata Rocco R   Picconi Barbara B   Calabresi Paolo P   De Leonibus Elvira E  

NPJ Parkinson's disease 20230616 1


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 o  ...[more]

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