Dataset Information

Alpha-Synuclein Pre-Formed Fibrils Injected into Prefrontal Cortex Primarily Spread to Cortical and Subcortical Structures.

ABSTRACT:

Background

Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by diffuse spread of alpha-synuclein (α-syn) throughout the brain. Patients with PDD and DLB have a neuropsychological pattern of deficits that include executive dysfunction, such as abnormalities in planning, timing, working memory, and behavioral flexibility. The prefrontal cortex (PFC) plays a major role in normal executive function and often develops α-syn aggregates in DLB and PDD.

Objective

To investigate the long-term behavioral and cognitive consequences of α-syn pathology in the cortex and characterize pathological spread of α-syn.

Methods

We injected human α-syn pre-formed fibrils into the PFC of wild-type male mice. We then assessed the behavioral and cognitive effects between 12- and 21-months post-injection and characterized the spread of pathological α-syn in cortical, subcortical, and brainstem regions.

Results

We report that PFC PFFs: 1) induced α-syn aggregation in multiple cortical and subcortical regions with sparse aggregation in midbrain and brainstem nuclei; 2) did not affect interval timing or spatial learning acquisition but did mildly alter behavioral flexibility as measured by intraday reversal learning; and 3) increased open field exploration.

Conclusions

This model of cortical-dominant pathology aids in our understanding of how local α-syn aggregation might impact some symptoms in PDD and DLB.

SUBMITTER: Weber MA

PROVIDER: S-EPMC10836574 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

Alpha-Synuclein Pre-Formed Fibrils Injected into Prefrontal Cortex Primarily Spread to Cortical and Subcortical Structures.

Weber Matthew A MA Kerr Gemma G Thangavel Ramasamy R Conlon Mackenzie M MM Gumusoglu Serena B SB Gupta Kalpana K Abdelmotilib Hisham A HA Halhouli Oday O Zhang Qiang Q Geerling Joel C JC Narayanan Nandakumar S NS Aldridge Georgina M GM

Journal of Parkinson's disease 20240101 1

<h4>Background</h4>Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by diffuse spread of alpha-synuclein (α-syn) throughout the brain. Patients with PDD and DLB have a neuropsychological pattern of deficits that include executive dysfunction, such as abnormalities in planning, timing, working memory, and behavioral flexibility. The prefrontal cortex (PFC) plays a major role in normal executive function and often develops α-syn aggregates in DLB and PDD.<h4 ...[more]

PMID: 38189765

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Dataset Information

Alpha-Synuclein Pre-Formed Fibrils Injected into Prefrontal Cortex Primarily Spread to Cortical and Subcortical Structures.

Background

Objective

Methods

Results

Conclusions

Publications

Alpha-Synuclein Pre-Formed Fibrils Injected into Prefrontal Cortex Primarily Spread to Cortical and Subcortical Structures.

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