Characterizing the protracted neurobiological and neuroanatomical effects of paraquat in a murine model of Parkinson's disease

Autor: Pragya Shail, Katelyn Ventura, Sheryl Beauchamp, Teresa Fortin, Shawn Hayley, Chris Rudyk, Carlos Torres, Zach Dwyer, Kyle Farmer, Kiara Ayoub, Alexa Derksen
Rok vydání: 2021
Předmět:
Male
Paraquat
0301 basic medicine
Aging
medicine.medical_specialty
Parkinson's disease
Protozoan Proteins
Substantia nigra
Proinflammatory cytokine
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
Animals
Pesticides
Inflammation
Microglia
business.industry
Pars compacta
Dopaminergic Neurons
General Neuroscience
Caspase 1
Dopaminergic
Neurodegeneration
Age Factors
NF-kappa B
Brain
Parkinson Disease
Milk Proteins
medicine.disease
Magnetic Resonance Imaging
Wiskott-Aldrich Syndrome Protein Family
3. Good health
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
Endocrinology
medicine.anatomical_structure
chemistry
Antigens
Surface
Neurology (clinical)
Geriatrics and Gerontology
Corticosterone
business
030217 neurology & neurosurgery
Developmental Biology
Zdroj: Neurobiology of Aging. 100:11-21
ISSN: 0197-4580
DOI: 10.1016/j.neurobiolaging.2020.11.013
Popis: The primary motor symptoms of Parkinson's disease (PD) result from the degeneration of dopamine-producing neurons of the substantia nigra pars compacta (SNc), and often, the loss is asymmetrical, resulting in unilateral tremor presentation. Notably, age is the primary risk factor for PD, and it is likely that the disease ultimately stems from the impact of environmental factors, which interact with the aging process. Recent research has focused on the role of microglia and pro-oxidative responses in dopaminergic neuronal death. In this study, we sought to examine the neurodegenerative, inflammatory, and stress effects of exposure to the etiologically relevant pesticide, paraquat, over time (up to 6 months after injections). We also were interested in whether a high-resolution, 7-Tesla animal magnetic resonance imaging would be sensitive enough to detect the degenerative impact of paraquat. We found that paraquat induced a loss of dopaminergic SNc neurons and activation of microglia that surprisingly did not change over 6 months after the last injection. A long-lasting reduction was evident for body weight, and alterations in organ (lung and heart) weight were evident, which reflect the peripheral impact of the toxicant. The microglial proinflammatory actin-remodeling factor, WAVE2, along with the inflammatory transcription factor, nuclear factor kappa B were also elevated within the brain. Remarkably, the stress hormone, corticosterone, was still significantly elevated 1 month after paraquat, whereas the inflammasome factor, caspase-1, and antigen presentation factor, MFG-E8, both displayed delayed rises after the 6-month time. Using high-resolution magnetic resonance imaging, we detected no striatal changes but modest hemispheric differences in the SNc and time-dependent volumetric enlargement of the ventricles in paraquat-treated mice. These data suggest that paraquat induces long-term nigrostriatal pathology (possibly asymmetric) and inflammatory changes and stress and trophic/apoptotic effects that appear to either increase with the passage of time or are evident for at least 1 month. In brief, paraquat may be a useful nonspecific means to model widespread stress and inflammatory changes related to PD or age-related disease in general, but not the progressive nature of such diseases.
Databáze: OpenAIRE
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