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

摘要: Dopamine loss and motor deficits in Parkinson’s disease typically commence unilaterally remain asymmetric for many years, raising the possibility that endogenous defenses slow cross-hemispheric transmission of pathology. It is well-established biological response to subtoxic stress prepares cells survive subsequent toxic challenges, a phenomenon known as preconditioning, tolerance, or adaptation. Here we demonstrate unilateral striatal infusions oxidative toxicant 6-hydroxydopamine (6-OHDA) precondition contralateral nigrostriatal pathway against toxicity second 6-OHDA infusion opposite hemisphere. 6-OHDA-induced dopaminergic terminals striatum was ablated by shown two independent markers phenotype, each measured blinded observers. Similarly, somata substantia nigra also abolished, according measurements. Motor asymmetries floor landings, forelimb contacts with wall, spontaneous turning behavior were consistent these histological observations. Unilateral increased phosphorylation kinase ERK2 expression antioxidant enzyme CuZn superoxide dismutase both striata, our previous mechanistic work showing proteins mediate preconditioning cells. These findings support existence suggest neurons mount impressive natural defenses, despite their reputation being vulnerable injury. If results generalize humans, pathology may progress slowly asymmetrically because exposure disease-precipitating insult induces bilateral upregulation elicits preconditioning.