The Impact of Mitochondrial Dysfunction on Dopaminergic Neurons in the Olfactory Bulb and Odor Detection

Understanding non-motor symptoms of Parkinson’s disease is important in order to unravel the underlying molecular mechanisms of the disease. Olfactory dysfunction is an early stage, non-motor symptom which occurs in 95% of Parkinson’s disease patients. Mitochondrial dysfunction is a key feature in P...

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Bibliographic Details
Published in:Molecular neurobiology 2020-09, Vol.57 (9), p.3646-3657
Main Authors: Paß, Thomas, Aßfalg, Marlene, Tolve, Marianna, Blaess, Sandra, Rothermel, Markus, Wiesner, Rudolf J., Ricke, Konrad M.
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Cell Biology
Dopamine receptors
Information processing
Mesencephalon
Mitochondria
Molecular modelling
Movement disorders
Neurobiology
Neurodegenerative diseases
Neurogenesis
Neurology
Neurons
Neurosciences
Odors
Olfaction
Olfactory bulb
Olfactory discrimination
Olfactory discrimination learning
Parkinson's disease
Progenitor cells
Smell
Stem cells
Substantia nigra
Subventricular zone
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Summary:Understanding non-motor symptoms of Parkinson’s disease is important in order to unravel the underlying molecular mechanisms of the disease. Olfactory dysfunction is an early stage, non-motor symptom which occurs in 95% of Parkinson’s disease patients. Mitochondrial dysfunction is a key feature in Parkinson’s disease and importantly contributes to the selective loss of dopaminergic neurons the substantia nigra pars compacta . The olfactory bulb, the first olfactory processing station, also contains dopaminergic neurons, which modulate odor information and thereby enable odor detection as well as odor discrimination. MitoPark mice are a genetic model for Parkinson’s disease with severe mitochondrial dysfunction, reproducing the differential vulnerability of dopaminergic neurons in the midbrain. These animals were used to investigate the impact of mitochondrial dysfunction on olfactory-related behavior and olfactory bulb dopaminergic neuron survival. Odor detection was severely impaired in MitoPark mice. Interestingly, only the small anaxonic dopaminergic subpopulation, which is continuously replenished by neurogenesis, was moderately reduced in number, much less compared with dopaminergic neurons in the midbrain. As a potential compensatory response, an enhanced mobilization of progenitor cells was found in the subventricular zone. These results reveal a high robustness of dopaminergic neurons located in the olfactory bulb towards mitochondrial impairment, in striking contrast to their midbrain counterparts.
ISSN:0893-7648
1559-1182
DOI:10.1007/s12035-020-01947-w