A Pilot Study of Ex Vivo Human Prefrontal RNA Transcriptomics in Parkinson's Disease

Parkinson's disease (PD) can dramatically change cortical neurophysiology. The molecular basis for PD-related cortical changes is unclear because gene expression data are usually derived from postmortem tissue collected at the end of a complex disease and they profoundly change in the minutes after death. Here, we studied cortical changes in tissue from the prefrontal cortex of living PD patients undergoing deep-brain stimulation implantation surgery. We examined 780 genes using the NanoString nCounter platform and found that 40 genes were differentially expressed between PD (n = 12) and essential tremor (ET; n = 9) patients. One of these 40 genes, STAT1, correlated with intraoperative 4-Hz rhythms and intraoperative performance of an oddball reaction-time task. Using a pre-designed custom panel of 780 targets, we compared these intraoperative data with those from a separate cohort of fresh-frozen tissue from the same frontal region in postmortem human PD donors (n = 6) and age-matched neurotypical controls (n = 6). This cohort revealed 279 differentially expressed genes. Fifteen of the 40 intraoperative PD-specific genes overlapped with postmortem PD-specific genes, including CALB2 and FOXP2. Transcriptomic analyses identified pathway changes in PD that had not been previously observed in postmortem cases. These molecular signatures of cortical function and dysfunction may help us better understand cognitive and neuropsychiatric aspects of PD.