Loss of dopamine disrupts circadian rhythms in a mouse model of Parkinson's disease
Open accessAbstract
Although a wide range of physiological functions regulated by dopamine (DA) display circadian variations, the role of DA in the generation and/or modulation of these rhythms is unknown. In Parkinson's disease (PD) patients, in addition to the classical motor symptoms, disturbances of the pattern of daily rest/wake cycles are common non-motor symptoms. We investigated daily and circadian rhythms of rest/activity behaviors in a transgenic MitoPark mouse model with selective inactivation of mitochondrial transcription factor A (Tfam) resulting in a slow and progressive degeneration of DA neurons in midbrain structures. Correlated with this, MitoPark mice show a gradual reduction in locomotor activity beginning at about 20weeks of age. In a light-dark cycle, MitoPark mice exhibit a daily pattern of rest/activity rhythms that shows an age-dependent decline in both the amplitude and the stability of the rhythm, coupled with an increased fragmentation of day/night activities. When the circadian system is challenged by exposure to constant darkness or constant light conditions, control littermates retain a robust free-running circadian locomotor rhythm, whereas in MitoPark mice, locomotor rhythms are severely disturbed or completely abolished. Re-exposure to a light/dark cycle completely restores daily locomotor rhythms. MitoPark mice and control littermates express similar masking behaviors under a 1h light/1h dark regime, suggesting that the maintenance of a daily pattern of rest/activity in arrhythmic MitoPark mice can be attributed to the acute inhibitory and stimulatory effects of light and darkness. These results imply that, in addition to the classical motor abnormalities observed in PD, the loss of the midbrain DA neurons leads to impairments of the circadian control of rest/activity rhythms.
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MitoPark transgenic mice show a profound disruption of locomotor rhythms in constant conditions and are more vulnerable to changes in the light-dark cycle.
“MitoPark transgenic mice also show a profound disruption of locomotor rhythms in constant conditions and are more vulnerable to changes in the light–dark cycle279.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [279]
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- Authors
- Fifel, K., & Cooper, H. M.
- Affiliations
- Inserm (FR)
- Corresponding author
- Fifel, Karim
- Cooper, Howard M.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 71
- Pages
- 359-369
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2057946202
- Cited by
- 80
- References
- 83
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 4 · 2023: 10 · 2022: 13 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 13 · 2016: 5 · 2015: 4 · 2014: 1
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fondation de France
- Rhône-Alpes Cible/CMIRA
- ANR-09-MNPS-040
- Retina France
- GDRI Neurosciences
- Cluster Handicap Vieillissement Neurosciences
- FRM
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- dopamine, circadian rhythm, Parkinson's disease, TFAM, dopaminergic neuron loss, rest-activity rhythm, locomotor activity, free-running rhythm, constant darkness, constant light, non-motor symptoms, midbrain dopaminergic neurons
- MeSH terms
- Activities of Daily Living, Age Factors, Animals, Disease Models, Animal, DNA-Binding Proteins, Dopamine, Mesencephalon, Mice, Transgenic, Motor Activity, Parkinson Disease, Transcription Factors, Chi-Square Distribution, Chronobiology Disorders, Mitochondrial Proteins, Dopamine Plasma Membrane Transport Proteins, Mice
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