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The rat rotenone model reproduces the abnormal pattern of central catecholamine metabolism found in Parkinson's disease
- Source :
- Disease Models & Mechanisms, article-version (VoR) Version of Record
- Publication Year :
- 2021
-
Abstract
- Recent reports indicate that Parkinson's disease (PD) involves specific functional abnormalities in residual neurons – decreased vesicular sequestration of cytoplasmic catecholamines via the vesicular monoamine transporter (VMAT) and decreased aldehyde dehydrogenase (ALDH) activity. This double hit builds up the autotoxic metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), the focus of the catecholaldehyde hypothesis for the pathogenesis of PD. An animal model is needed that reproduces this abnormal catecholamine neurochemical pattern. Adult rats received subcutaneous vehicle or the mitochondrial complex 1 inhibitor rotenone (2 mg/kg/day via a minipump) for 10 days. Locomotor activity was recorded, and striatal tissue sampled for catechol contents and catechol ratios that indicate the above abnormalities. Compared to vehicle, rotenone reduced locomotor activity (P=0.002), decreased tissue dopamine concentrations (P=0.00001), reduced indices of vesicular sequestration (3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine) and ALDH activity (DOPAC/DOPAL) (P=0.0025, P=0.036), and increased DOPAL levels (P=0.04). The rat rotenone model involves functional abnormalities in catecholaminergic neurons that replicate the pattern found in PD putamen. These include a vesicular storage defect, decreased ALDH activity and DOPAL build-up. The rat rotenone model provides a suitable in vivo platform for studying the catecholaldehyde hypothesis.<br />Summary: This study presents an animal model that reflects the neurochemical pattern found in Parkinson's patients, the basis of the new and evolving catecholaldehyde hypothesis for the disease.
- Subjects :
- medicine.medical_specialty
Parkinson's disease
Dopamine
Neurodegenerative Disorders
Neuroscience (miscellaneous)
Medicine (miscellaneous)
Aldehyde dehydrogenase
General Biochemistry, Genetics and Molecular Biology
chemistry.chemical_compound
Norepinephrine
Neurochemical
Catecholamines
Immunology and Microbiology (miscellaneous)
Internal medicine
Rotenone
medicine
Animals
Rat as a Disease Model
Resource Article
Vesicular uptake
biology
Chemistry
Parkinson Disease
Lewy body diseases
medicine.disease
Rats
Vesicular monoamine transporter
Endocrinology
DOPAL
Catechol
Catecholamine
biology.protein
3,4-Dihydroxyphenylacetic Acid
Catecholaminergic cell groups
medicine.drug
Subjects
Details
- ISSN :
- 17548411
- Volume :
- 15
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Disease modelsmechanisms
- Accession number :
- edsair.doi.dedup.....aac6d6e016f5d8b47ffeb083fd5c6391