Early Parkinson ’s disease and mechanisms compensating for dopaminergic neurons loss-an energy metabolism point of view

• Autorzy: Kuter K.
• Języki publikacji: EN

Abstrakty

EN

Degeneration of dopaminergic neurons in substantia nigra (SN) is underlying cause of movement disorder observed in Parkinson’s disease.At its early stages motor deficits are masked by compensatory mechanisms. Our aim was to describe how prolonged metabolic dysfunction of astrocytes would influence processes of compensation for the dopaminergic neurons degeneration. Rat model of selective nigrostriatal dopaminergic system degeneration was induced by intracerebral injection of 6-OHDA into medial forebrain bundle. Astrocytes metabolic dysfunction was induced by 7-days infusion of fluorocitrate (FC) into SN. Dopaminergic neurons lesioning as well as astrocytes dysfunction induced motor deficits that were reversed with time, despite progressing neuronal degeneration after 6-OHDA. Inhibition of astrocytes metabolism by FC caused tendency to decrease performance of not-assembled complex I and IV. Double toxicity of 6-OHDA and FC also decreased performance in complex I and IV especially 4 weeks after operations and FC discontinuation, causing also significant decrease in specific activity of complex IV. Along with those changes, we observed decreased mitochondrial membranes viscosity. Results from aconitase activity showed that when neurons were devoid of astrocytes support, their aconitase activity increased drastically. Presented research shows that prolonged dysfunction of astrocytes influences dopaminergic cells metabolism and vulnerability. Surprisingly, changes in oxidative phosphorylation system were shown very small even after loss of 33% to 61% of dopaminergic neurons – what would suggest extensive adaptive possibilities, maybe in mitochondria volume. Supported by the Statutory Funds of the Institute of Pharmacology, PAS, Poland; Technische Universität Darmstadt, MOBILNOŚĆ PLUS MNiSW scholarship and NCN grant nr 2012/05/B/ NZ4/02599

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S16

Twórcy

autor

Kuter K.

• Physical Biochemistry, Department of Chemistry, Darmstadt University of Technology, Darmstadt, Germany
• Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland