Whole transcriptome profiling of the MPTP neurotoxic mice model reveals potential targets to modulate gene expression

1-methyl-4-phenyl-1,2,4,6,-tetrahydropyridine (MPTP) is a neurotoxin that selectively targets the dopaminergic system in the substantia nigra pars compacta (SNpc). The administration of MPTP results in Parkinsonism-like symptoms and is therefore commonly used as a rodent model to gain insight into the pathology of Parkinson’s disease (PD). In this study, the SNpc from previously characterised MPTP-lesioned mice was evaluated using Next-Generation whole transcriptome sequencing. The investigative power of combined genome-wide sequencing and bioinformatics analyses used in this study provide a detailed and unbiased examination into the genes altered in this model. In silico analysis of transcriptomic data identified neurobiological functions, processes and pathways implicated in mice after MPTP lesioning. Differentially expressed (DE) genes were identified in the MPTP-lesioned mice that are known to exhibit binding and transporter activity associated with biological processes related to brain and cognitive development, neuroplasticity, regulation and cellular response in PD patients. Pathway enrichment analysis on these DE genes indicates an impairment of dopamine synthesis and perturbed synaptic neurotransmission. Genes previously associated with PD were detected in this neurotoxin model which validates the use of this mice model in PD research. This approach using whole transcriptome sequencing identified gene alterations that may be involved in the etiology of PD and can be used to develop potential neuroprotective and therapeutic drugs . In addition, key regulatory genes involved in maintaining the brain blood barrier and promoting neurogenesis were identified.