Cingulate networks associated with gray matter loss in Parkinson's disease show high expression of cholinergic genes in the healthy brain. (4th May 2021)

• Record Type: Journal Article
• Authors: Keo, Arlin; Dzyubachyk, Oleh; van der Grond, Jeroen; Hafkemeijer, Anne; van de Berg, Wilma D.J.; van Hilten, Jacobus J.; Reinders, Marcel J.T.; Mahfouz, Ahmed
• Is Part Of: European journal of neuroscience. Volume 53:Number 11(2021)
• Page Start: 3727
• Page End: 3739
• Publication Date: 2021-05-04
• Subjects: Allen Human Brain Atlas -- brain imaging -- neuroinformatics -- spatial transcriptomics -- structural covariance networks; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.15216
• Languages: English
• ISSNs: 0953-816X

Abstract

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. Abstract : Earlier magnetic resonance imaging (MRI) studies identified brain networks referred to as structural covariance networks (SCNs) for which two were associated with gray matter loss in Parkinson's disease: the posterior cingulate network and anterior cingulate network. We combined the spatial information from these networks with brain‐wide healthy transcriptomic data from the Allen Human Brain Atlas and found that genes related to the cholinergic system, alcohol and drug withdrawal symptoms, and multiple signaling events, were highly expressed within these brain networks.