Functional genomic analysis of non-immunosuppressant neuroimmunophilin ligand in a rat Parkinson's model.

摘要

Parkinson's disease (PD) is a neurodegenerative disorder with the loss of substantia nigra, pars compacts (SNc) neurons as its main pathology. Novel treatments for PD include administration of non-immunosuppressant derivatives of neuroimmunophilin ligands (NILs), such as GPI-1046. Here, we investigate mRNA changes in the striatum of a 6-hydroxydopamine (6-OHDA) model of PD after treatment with GPI-1046, using National Institutes of Health NH) 15K mouse probes with two-colour DNA microarray hybridization. We compared the effects of lesioning, treatment and the interaction effects of lesioning and treatment using a 2 x 2 factorial microarray design. Significant changes were observed when comparing lesioning to GPI-1046 treatment but not with both lesioning and treatment. Quantitative polymerase chain reaction (QPCR) was used to confirm the direct interaction of lesioning and treatment versus no lesion and vehicle only treatment. A surprising result of the QPCR assay was a substantial increase in Presenilin 1 in the lesioned treated tissue in a majority of the animals tested.