Increased energetic demand supported by mitochondrial electron transfer chain and astrocyte assistance is essential to maintain the compensatory ability of the dopaminergic neurons in an animal model of early Parkinson's disease

• Published in: Mitochondrion Vol. 47; pp. 227 - 237
• Main Authors: Kuter, Katarzyna Z, Olech, Łukasz, Dencher, Norbert A
• Format: Journal Article
• Language: English
• Published: Netherlands 01-07-2019
• Subjects: Animals; Astrocytes - enzymology; Astrocytes - pathology; Dopaminergic Neurons - enzymology; Electron Transport Chain Complex Proteins - metabolism; Epigenesis, Genetic; Male; Mitochondria - metabolism; Mitochondria - pathology; Parkinson Disease, Secondary - chemically induced; Parkinson Disease, Secondary - enzymology; Parkinson Disease, Secondary - pathology; Rats; Rats, Wistar; Energy metabolism; Succinate dehydrogenase; Parkinson's disease; Neurodegeneration; Supramolecular complexes; Adaptation
• ISSN: 1567-7249; 1872-8278
• DOI: 10.1016/j.mito.2018.12.002

Partial degeneration of dopaminergic neurons in the substantia nigra (SN), induces locomotor disability in animals but with time it is spontaneously compensated for by neurons surviving in the tissue by increasing their functional efficiency. Such compensation probably increases energy requirements and astrocyte support could be essential for this ability. We studied the effect of degeneration of dopaminergic neurons induced by the selective toxin 6-hydroxydopamine and/or death of 30% of astrocytes induced by chronic infusion of the glial toxin fluorocitrate on functioning of the mitochondrial electron transfer chain (ETC) complexes (Cxs) I, II, IV and their higher assembled forms, supercomplexes in the rat SN. Astrocyte death decreased Cx I and IV performance, while significantly increased the amount of Cx II protein SDHA, indicating system adaptation. After death of 50% of dopaminergic neurons in the SN, we observed increased mitochondrial Cxs performing, especially Cx I and IV in the remaining cells. It corresponded with reduction of behavioural deficits. Those results support the hypothesis that the compensatory ability of surviving neurons requires meeting their higher energetic demand by ETC. When astrocytes were defective, the neurons remaining after partial lesion were not able to enhance their functioning anymore and compensate for deficits. It proves in vivo that astrocytic support is important for compensatory potential of neurons in the SN. Neuro-glia cooperation is fundamental for compensation for early deficits in the nigrostriatal system.