Whole-Transcriptome Analysis of Mouse Models with MPTP-Induced Early Stages of Parkinson's Disease Reveals Stage-Specific Response of Transcriptome and a Possible Role of Myelin-Linked Genes in Neurodegeneration

Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons. A whole-transcriptome analysis of the substantia nigra and striatum of an MPTP-induced mouse models of the earliest stages of PD was performed. Functional clustering of differentially represented transcripts revealed processes associated with the functioning of synapses, dendrites, axons, and myelination of neuronal projections. All of these processes occur in both the substantia nigra and striatum, but they are aimed at the functioning of neuron terminals in the striatum. One cluster was identified at the earliest stage modeled, i.e., "neuron projection" in the substantia nigra and "transport" in the striatum, and their number increased at subsequent stages. The number of clusters in the striatum predominates over those in the substantia nigra and there is a pronounced increase in the number of clusters from the modeled early stages to the late stages. These findings indicate that the substantia nigra and striatum have unique patterns of changes at each stage. Considering the clustering of individual processes, it was seen that there is a set of hierarchical clusters that overlap only partially at different stages and in different tissues. The data indicate a consistent involvement of the transcriptome in the pathogenesis of PD and highlight the independent role of various brain structures and individual parts of nerve cells in the formation of a response to the development of neurodegeneration. Decreased myelination of neuronal projections may be associated with the development of PD in the models considered.