Evidence for cross-hemispheric preconditioning in experimental Parkinson's disease

Brain Structure & Function
Justin N WeilnauRehana K Leak

Abstract

Dopamine loss and motor deficits in Parkinson's disease typically commence unilaterally and remain asymmetric for many years, raising the possibility that endogenous defenses slow the cross-hemispheric transmission of pathology. It is well-established that the biological response to subtoxic stress prepares cells to survive subsequent toxic challenges, a phenomenon known as preconditioning, tolerance, or stress adaptation. Here we demonstrate that unilateral striatal infusions of the oxidative toxicant 6-hydroxydopamine (6-OHDA) precondition the contralateral nigrostriatal pathway against the toxicity of a second 6-OHDA infusion in the opposite hemisphere. 6-OHDA-induced loss of dopaminergic terminals in the contralateral striatum was ablated by cross-hemispheric preconditioning, as shown by two independent markers of the dopaminergic phenotype, each measured by two blinded observers. Similarly, loss of dopaminergic somata in the contralateral substantia nigra was also abolished, according to two blinded measurements. Motor asymmetries in floor landings, forelimb contacts with a wall, and spontaneous turning behavior were consistent with these histological observations. Unilateral 6-OHDA infusions increased phosphorylation of t...Continue Reading

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Citations

Oct 16, 2018·Frontiers in Molecular Neuroscience·Johannes BurtscherChristoph Schwarzer
Aug 25, 2018·Dose-response : a Publication of International Hormesis Society·Rehana K LeakMelvin E Andersen
Aug 31, 2021·Neurobiology of Disease·Vishakh IyerThyagarajan Subramanian

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Methods Mentioned

BETA
electrophoresis

Software Mentioned

ImageStudio
SPSS

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