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Neuronal Expression of Familial Parkinson's Disease A53T α-Synuclein Causes Early Motor Impairment, Reduced Anxiety and Potential Sleep Disturbances in Mice
- Source :
- Journal of Parkinson's Disease. 3:215-229
- Publication Year :
- 2013
- Publisher :
- IOS Press, 2013.
-
Abstract
- Background Mutations in the human α-synuclein gene lead to early-onset Parkinson's disease (PD); however, phenotypes of α-synuclein mutant mice vary depending upon the promoter driving transgene expression. Objective The goal of this study was to characterize behavior and neurochemical alterations in mice expressing mutant (A53T) human α-synuclein, controlled by a neuron-specific Thy-1 promoter. Our data provide important additional phenotypic and biochemical characterization of a previously generated model of PD. Methods A53T (SNCA) and wild type (WT) littermate mice were evaluated for motor function (rotarod and stride length) and anxiety (elevated plus maze and open field) every 2 weeks. At 24 weeks mice were evaluated in a Comprehensive Lab Animal Monitoring System (CLAMS). A separate cohort of mice were euthanized at 12, 24 and 36 weeks for immunoblot analysis of α-synuclein, dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the striatum, and hypothalamic serotonin and metabolites were measured. Results SNCA mice display significant motor deficits at 14-18 weeks of age compared to WT mice, which progress over time. CLAMS analysis revealed an increase in activity during the dark phase and a reduction in overall estimated sleep time for SNCA mice compared to WT consistent with clinical reports of sleep abnormalities in PD. A transient change in the levels of DAT appeared at 12 weeks in the striatum and serotonin levels were also altered in the hypothalamus at this time point. Conclusions This PD model displays consistent and clinically relevant motor and sleep phenotypes. Anxiety phenotypes are consistent with other α-synuclein based PD models yet incongruous with typical clinical symptoms. Early increases in serotonin levels potentially explain reductions in anxiety behaviors and sleep.
- Subjects :
- Sleep Wake Disorders
medicine.medical_specialty
Elevated plus maze
Parkinson's disease
Tyrosine 3-Monooxygenase
Mice, Transgenic
Striatum
Anxiety
Open field
Mice
Cellular and Molecular Neuroscience
Neurochemical
Intermediate Filament Proteins
Dopamine
Internal medicine
medicine
Animals
Humans
Maze Learning
Dopamine transporter
Dopamine Plasma Membrane Transport Proteins
biology
Tyrosine hydroxylase
business.industry
Age Factors
Brain
Parkinson Disease
medicine.disease
Disease Models, Animal
Endocrinology
Gene Expression Regulation
Mutation
Exploratory Behavior
biology.protein
Neurology (clinical)
business
Psychomotor Performance
medicine.drug
Subjects
Details
- ISSN :
- 1877718X and 18777171
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of Parkinson's Disease
- Accession number :
- edsair.doi.dedup.....09b37b71f4daa53ae05ec08b79fd366b