Transcription profiling of mouse models or Parkinsons disease reveal miRNAs and codon usage regulate striatal gene and protein expression

The molecular mechanisms underlying the changes in the nigrostriatal pathway in Parkinson’s disease (PD) are not completely understood. Here we use microarrays and mass spectrometry to study the transcriptomic and proteomic changes in the striatum of two mouse models of PD induced by distinct neurotoxins, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Transcripts and proteins were found with similar abundance changes in both models which may be involved in the pathophysiology of PD. GFAP transcript and protein levels were significantly up-regulated by both neurotoxins, confirming the known astrocytic response to these drugs. Other genes and proteins were idiosyncratic in their responses to the two toxins, suggesting specific toxicological responses. Comparing transcript and protein levels revealed that efficiently translated genes used more commonly occurring codons than inefficiently translated genes. Additionally, a potential role was found for miRNAs in translational control in the striatum. The results constitute one of the largest datasets integrating transcript and protein changes for these two neurotoxin models with many similar endpoint phenotypes but distinct pathologies. Using multiple toxins while examining proteins and transcripts can be an effective method of delineating the molecular pathology of neurodegenerative diseases. Experiment Overall Design: Parkinson's disease mouse models were created by injecting male C57BL/6J mice with either Methamphetamine or MPTP and were compared to saline injected controls. 3 biological replicates were examined for each condition yielding 9 total samples. Single channel Affymetrix mouse expression arrays 430_2 were used to analyze gene expression in the striata of each mouse.