Journal article
Cortical alpha-synuclein preformed fibrils do not affect interval timing in mice
Neuroscience letters, Vol.765, 136273
09/30/2021
DOI: 10.1016/j.neulet.2021.136273
PMCID: PMC8577190
PMID: 34601038
Abstract
•Cortical injection of alpha-synuclein preformed fibrils (PFF) induces diffuse synucleinopathy.•Cortical injection of PFFs do not affect interval timing in mice.•Medial prefrontal cortical synucleinopathy does not reliably disrupt interval timing.
One hallmark feature of Parkinson’s disease (PD) is Lewy body pathology associated with misfolded alpha-synuclein. Previous studies have shown that striatal injection of alpha-synuclein preformed fibrils (PFF) can induce misfolding and aggregation of native alpha-synuclein in a prion-like manner, leading to cell death and motor dysfunction in mouse models. Here, we tested whether alpha-synuclein PFFs injected into the medial prefrontal cortex results in deficits in interval timing, a cognitive task which is disrupted in human PD patients and in rodent models of PD. We injected PFF or monomers of human alpha-synuclein into the medial prefrontal cortex of mice pre-injected with adeno-associated virus (AAV) coding for overexpression of human alpha-synuclein or control protein. Despite notable medial prefrontal cortical synucleinopathy, we did not observe consistent deficits in fixed-interval timing. These results suggest that cortical alpha-synuclein does not reliably disrupt fixed-interval timing.
Details
- Title: Subtitle
- Cortical alpha-synuclein preformed fibrils do not affect interval timing in mice
- Creators
- Qiang ZhangHisham AbdelmotilibTravis LarsonCameron KeomanivongMackenzie ConlonGeorgina M AldridgeNandakumar S Narayanan
- Resource Type
- Journal article
- Publication Details
- Neuroscience letters, Vol.765, 136273
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.neulet.2021.136273
- PMID
- 34601038
- PMCID
- PMC8577190
- ISSN
- 0304-3940
- eISSN
- 1872-7972
- Grant note
- DOI: 10.13039/100000002, name: NIH
- Language
- English
- Date published
- 09/30/2021
- Academic Unit
- Neurology; Iowa Neuroscience Institute
- Record Identifier
- 9984181074102771
Metrics
27 Record Views