Journal article
Alpha-Synuclein Pre-Formed Fibrils Injected into Prefrontal Cortex Primarily Spread to Cortical and Subcortical Structures
Journal of Parkinson's disease, Vol.14(1), pp.81-94
2024
DOI: 10.3233/JPD-230129
PMCID: PMC10836574
PMID: 38189765
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.
Details
- Title: Subtitle
- Alpha-Synuclein Pre-Formed Fibrils Injected into Prefrontal Cortex Primarily Spread to Cortical and Subcortical Structures
- Creators
- Matthew A. Weber - University of IowaGemma Kerr - University of IowaRamasamy Thangavel - University of IowaMackenzie M. Conlon - University of IowaSerena B. Gumusoglu - University of IowaKalpana Gupta - Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA, USAHisham A. Abdelmotilib - University of IowaOday Halhouli - University of IowaQiang Zhang - University of IowaJoel C. Geerling - University of IowaNandakumar S. Narayanan - University of IowaGeorgina M. Aldridge - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of Parkinson's disease, Vol.14(1), pp.81-94
- DOI
- 10.3233/JPD-230129
- PMID
- 38189765
- PMCID
- PMC10836574
- ISSN
- 1877-7171
- eISSN
- 1877-718X
- Language
- English
- Electronic publication date
- 12/30/2023
- Date published
- 2024
- Academic Unit
- Neurology; Iowa Neuroscience Institute; Obstetrics and Gynecology
- Record Identifier
- 9984539528202771
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