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
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Abstract
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.