Parkinson's Disease is Associated with Dysregulations of a Dopamine-Modulated Gene Network Relevant to Sleep and Affective Neurobehaviors in the Striatum

Sci Rep. 2019 Mar 18;9(1):4808. doi: 10.1038/s41598-019-41248-4.


In addition to the characteristic motor symptoms, Parkinson's disease (PD) often involves a constellation of sleep and mood symptoms. However, the mechanisms underlying these comorbidities are largely unknown. We have previously reconstructed gene networks in the striatum of a population of (C57BL/6J x A/J) F2 mice and associated the networks to sleep and affective phenotypes, providing a resource for integrated analyses to investigate perturbed sleep and affective functions at the gene network level. Combining this resource with PD-relevant transcriptomic datasets from humans and mice, we identified four networks that showed elevated gene expression in PD patients, including a circadian clock and mitotic network that was altered similarly in mouse models of PD. We then utilized multiple types of omics data from public databases and linked this gene network to postsynaptic dopamine signaling in the striatum, CDK1-modulated transcriptional regulation, and the genetic susceptibility of PD. These findings suggest that dopamine deficiency, a key aspect of PD pathology, perturbs a circadian/mitotic gene network in striatal neurons. Since the normal functions of this network were relevant to sleep and affective behaviors, these findings implicate that dysregulation of functional gene networks may be involved in the emergence of non-motor symptoms in PD. Our analyses present a framework for integrating multi-omics data from diverse sources in mice and humans to reveal insights into comorbid symptoms of complex diseases.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Affective Symptoms / genetics*
  • Affective Symptoms / pathology
  • Affective Symptoms / physiopathology
  • Animals
  • CDC2 Protein Kinase / metabolism
  • Circadian Clocks / genetics
  • Corpus Striatum / cytology
  • Corpus Striatum / pathology*
  • Corpus Striatum / physiopathology
  • Datasets as Topic
  • Disease Models, Animal
  • Dopamine / deficiency*
  • Dopaminergic Neurons / pathology
  • Gene Expression Profiling
  • Gene Expression Regulation / physiology
  • Gene Regulatory Networks / physiology*
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Mice
  • Parkinson Disease / genetics*
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology
  • Sleep / genetics*
  • Transcription, Genetic


  • CDC2 Protein Kinase
  • CDK1 protein, human
  • Cdk1 protein, mouse
  • Dopamine