Journal article
Chronic corticosterone aggravates behavioral and neuronal symptomatology in a mouse model of alpha-synuclein pathology.
- Burtscher J Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, EPFL, Lausanne, Switzerland.
- Copin JC Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, EPFL, Lausanne, Switzerland.
- Rodrigues J Laboratory of Behavioral Genetics, Brain Mind Institute, EPFL, Lausanne, Switzerland.
- Kumar ST Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, EPFL, Lausanne, Switzerland.
- Chiki A Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, EPFL, Lausanne, Switzerland.
- Guillot de Suduiraut I Laboratory of Behavioral Genetics, Brain Mind Institute, EPFL, Lausanne, Switzerland.
- Sandi C Laboratory of Behavioral Genetics, Brain Mind Institute, EPFL, Lausanne, Switzerland.
- Lashuel HA Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, EPFL, Lausanne, Switzerland. Electronic address: hilal.lashuel@epfl.ch.
- 2019-10-05
Published in:
- Neurobiology of aging. - 2019
Chronic stress
Conditioning
Depression
Neurodegeneration
Parkinson's disease
Synuclein
Animals
Behavior, Animal
Brain
Corticosterone
Disease Models, Animal
Dopaminergic Neurons
Male
Mice, Inbred C57BL
Parkinson Disease
Synucleinopathies
alpha-Synuclein
English
Debilitating, yet underinvestigated nonmotor symptoms related to mood/emotion, such as depression, are common in Parkinson's disease. Here, we explore the role of depression and of the amygdala, a brain region robustly linked to mood/emotion, in synucleinopathy. We hypothesized that mood/emotional deficits might accelerate Parkinson's disease-linked symptomatology, including the formation of α-synuclein pathology. We combined elevated corticosterone treatment, modeling chronic stress and depression, with a model of seeded α-synuclein pathology in mouse striatum and assessed behavioral parameters with a focus on mood/emotion, and neuropathology. We report behavioral resilience against α-synuclein proteinopathy in the absence of additional insults, potentially based on hormesis/conditioning mechanisms. Elevated corticosterone, however, reversed α-synuclein pathology-induced behavioral adaptations and was associated with increased dopaminergic cell loss as well as aggravated α-synuclein pathology in specific brain regions, such as the entorhinal cortex. These findings point to elevated glucocorticoids as a risk factor for Parkinson's disease progression and highlight the potential of glucocorticoid level reducing strategies to slow down disease progression in synucleinopathy.
- Language
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- English
- Open access status
- hybrid
- Identifiers
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- DOI 10.1016/j.neurobiolaging.2019.08.007
- PMID 31585362
- Persistent URL
- https://folia.unifr.ch/global/documents/10234
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