Targeted Ablation of Primary Cilia in Differentiated Dopaminergic Neurons Reduces Striatal Dopamine and Responsiveness to Metabolic Stress
| Autor: | Grzegorz Kreiner, Nadja Mannal, Rasem Mustafa, Björn Spittau, Joachim Kirsch, Kerry L. Tucker, Rosanna Parlato, Rüstem Yilmaz, Christina Pötschke, Chahinaz Rawas, Katarzyna Kamińska, Birgit Liss |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
DDC 540 / Chemistry & allied sciences
Physiology Dopamine striatum Clinical Biochemistry intraflagellary protein Substantia nigra Striatum RM1-950 Biochemistry Article Corpus striatum chemistry.chemical_compound DDC 570 / Life sciences ddc:570 Ciliogenesis Schrittmacher medicine Neurotoxin Molecular Biology Autoreceptors multielecotrode arrays (MEA) Chemistry Cilium MPTP Dopaminergic D2-autoreceptor Cell Biology DDC 600 / Technology (Applied sciences) pacemaker Cell biology substantia nigra nervous system ddc:540 Dopamin Therapeutics. Pharmacology dopamine ddc:600 medicine.drug primary cilium |
| Zdroj: | Antioxidants, Vol 10, Iss 1284, p 1284 (2021) Antioxidants Volume 10 Issue 8 |
| Popis: | Primary cilia (PC) are microtubule-based protrusions of the cell membrane transducing molecular signals during brain development. Here, we report that PC are required for maintenance of Substantia nigra (SN) dopaminergic (DA) neurons highly vulnerable in Parkinson’s disease (PD). Targeted blockage of ciliogenesis in differentiated DA neurons impaired striato-nigral integrity in adult mice. The relative number of SN DA neurons displaying a typical auto-inhibition of spontaneous activity in response to dopamine was elevated under control metabolic conditions, but not under metabolic stress. Strikingly, in the absence of PC, the remaining SN DA neurons were less vulnerable to the PD neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP). Our data indicate conserved PC-dependent neuroadaptive responses to DA lesions in the striatum. Moreover, PC control the integrity and dopamine response of a subtype of SN DA neurons. These results reinforce the critical role of PC as sensors of metabolic stress in PD and other disorders of the dopamine system. publishedVersion |
| Databáze: | OpenAIRE |
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