Abstract

Structural covariance networks are able to identify functionally organized brain regions by gray matter volume covariance across a population. We examined the transcriptomic signature of such anatomical networks in the healthy brain using postmortem microarray data from the Allen Human Brain Atlas. A previous study revealed that a posterior cingulate network and anterior cingulate network showed decreased gray matter in brains of Parkinson's disease patients. Therefore, we examined these two anatomical networks to understand the underlying molecular processes that may be involved in Parkinson's disease. Whole brain transcriptomics from the healthy brain revealed upregulation of genes associated with serotonin, GPCR, GABA, glutamate, and RAS‐signaling pathways. Our results also suggest involvement of the cholinergic circuit, in which genes NPPA, SOSTDC1, and TYRP1 may play a functional role. Finally, both networks were enriched for genes associated with neuropsychiatric disorders that overlap with Parkinson's disease symptoms. The identified genes and pathways contribute to healthy functions of the posterior and anterior cingulate networks and disruptions to these functions may in turn contribute to the pathological and clinical events observed in Parkinson's disease.

Highlights

  • Parkinson's disease (PD) is a neurodegenerative disorder characterized by the impairment of diverse motor and nonmotor symptoms that get progressively worse over time (Goedert et al, 2012)

  • For differential expression analysis we focused on the posterior cingulate network (Network C) and anterior cingulate network (Network D) that were previously associated with gray matter loss in PD

  • We examined transcriptomic signatures of the healthy brain in brain regions defined by SCNs that were identified in an earlier imaging analysis study (Hafkemeijer et al, 2014)

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Summary

Funding information

The Netherlands Technology Foundation (STW); The Dutch Research Council (NWO); Alzheimer Netherlands; LECMA; Amsterdam Neuroscience; Dutch Research council (ZonMW); Stichting Parkinson Fonds; Alzheimer association; MJ Fox foundation and Rotary Aalsmeer-­Uithoorn

| INTRODUCTION
| MATERIALS AND METHODS
| RESULTS
| DISCUSSION
CONFLICT OF INTEREST
Full Text
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