Preserved striatal innervation maintains motor function despite severe loss of nigral dopaminergic neurons.
- Resource Type
- Academic Journal
- Authors
- Paß T; Center for Physiology and Pathophysiology, Institute of Vegetative Physiology, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.; Ricke KM; Center for Physiology and Pathophysiology, Institute of Vegetative Physiology, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.; Hofmann P; Center for Physiology and Pathophysiology, Institute of Vegetative Physiology, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.; Chowdhury RS; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.; Nie Y; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.; Chinnery P; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.; Endepols H; University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, Cologne, Germany.; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Nuclear Medicine, Cologne, Germany.; Neumaier B; University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, Cologne, Germany.; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, Jülich, Germany.; Max Planck Institute for Metabolism Research, Cologne, Germany.; Carvalho A; Max Planck Institute for Metabolism Research, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD) and Centre for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany.; Rigoux L; Max Planck Institute for Metabolism Research, Cologne, Germany.; Steculorum SM; Max Planck Institute for Metabolism Research, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD) and Centre for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany.; Prudent J; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.; Riemer T; Department of Paediatrics and Adolescent Medicine, Experimental Neonatology, Faculty of Medicine, University of Cologne, Cologne, Germany.; Aswendt M; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Neurology, Cologne, Germany.; Liss B; Institute of Applied Physiology, University of Ulm, Ulm, Germany.; Brachvogel B; Department of Paediatrics and Adolescent Medicine, Experimental Neonatology, Faculty of Medicine, University of Cologne, Cologne, Germany.; Wiesner RJ; Center for Physiology and Pathophysiology, Institute of Vegetative Physiology, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD) and Centre for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany.
- Source
- Publisher: Oxford University Press Country of Publication: England NLM ID: 0372537 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2156 (Electronic) Linking ISSN: 00068950 NLM ISO Abbreviation: Brain Subsets: MEDLINE
- Subject
- Language
- English
Degeneration of dopaminergic neurons in the substantia nigra and their striatal axon terminals causes cardinal motor symptoms of Parkinson's disease. In idiopathic cases, high levels of mitochondrial DNA alterations leading to mitochondrial dysfunction are a central feature of these vulnerable neurons. Here we present a mouse model expressing the K320E-variant of the mitochondrial helicase Twinkle in dopaminergic neurons, leading to accelerated mitochondrial DNA mutations. These K320E-TwinkleDaN mice showed normal motor function at 20 months of age, although ∼70% of nigral dopaminergic neurons had perished. Remaining neurons still preserved ∼75% of axon terminals in the dorsal striatum and enabled normal dopamine release. Transcriptome analysis and viral tracing confirmed compensatory axonal sprouting of the surviving neurons. We conclude that a small population of substantia nigra dopaminergic neurons is able to adapt to the accumulation of mitochondrial DNA mutations and maintain motor control.
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