We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Preserved striatal innervation maintains motor function despite severe loss of nigral dopaminergic neurons.
- Authors
Paß, Thomas; Ricke, Konrad M; Hofmann, Pierre; Chowdhury, Roy S; Nie, Yu; Chinnery, Patrick; Endepols, Heike; Neumaier, Bernd; Carvalho, André; Rigoux, Lionel; Steculorum, Sophie M; Prudent, Julien; Riemer, Trine; Aswendt, Markus; Liss, Birgit; Brachvogel, Bent; Wiesner, Rudolf J
- Abstract
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.
- Subjects
DOPAMINERGIC neurons; MITOCHONDRIAL DNA; SUBSTANTIA nigra; PARKINSON'S disease; INNERVATION
- Publication
Brain: A Journal of Neurology, 2024, Vol 147, Issue 9, p3189
- ISSN
0006-8950
- Publication type
Article
- DOI
10.1093/brain/awae089