Transcriptional network analysis in frontal cortex in Lewy body diseases with focus on dementia with Lewy bodies.
The present study investigates global transcriptional changes in frontal cortex area 8 in incidental Lewy Body disease (iLBD), Parkinson disease (PD) and Dementia with Lewy bodies (DLB). We identified different coexpressed gene sets associated with disease stages, and gene ontology categories enriched in gene modules and differentially expressed genes including modules or gene clusters correlated to iLBD comprising upregulated dynein genes and taste receptors, and downregulated innate inflammation. Focusing on DLB, we found modules with genes significantly enriched in functions related to RNA and DNA production, mitochondria and energy metabolism, purine metabolism, chaperone and protein folding system and synapses and neurotransmission (particularly the GABAergic system). The expression of more than fifty selected genes was assessed with real time quantitative polymerase chain reaction. Our findings provide, for the first time, evidence of molecular cortical alterations in iLBD and involvement of several key metabolic pathways and gene hubs in DLB which may underlie cognitive impairment and dementia.
Department of Neurobiology, Yale School of Medicine, New Haven, CT.|Department of Experimental and Health Sciences, IBE, Institute of Evolutionary Biology, Universitat Pompeu Fabra-CSIC, Barcelona, Spain.
Gabriel
G
Santpere
Department of Pathology and Experimental Therapeutics, University of Barcelona, L'Hospitalet de Llobregat, Spain.
Paula
P
Garcia-Esparcia
Department of Pathology and Experimental Therapeutics, University of Barcelona, L'Hospitalet de Llobregat, Spain.
Pol
P
Andres-Benito
Department of Neurobiology, Yale School of Medicine, New Haven, CT.|Department of Experimental and Health Sciences, IBE, Institute of Evolutionary Biology, Universitat Pompeu Fabra-CSIC, Barcelona, Spain.
Belen
B
Lorente-Galdos
Department of Experimental and Health Sciences, IBE, Institute of Evolutionary Biology, Universitat Pompeu Fabra-CSIC, Barcelona, Spain.|Institute of Science and Technology, Centre for Genomic Regulation (CRG), Barcelona, Spain.|National Institute for Bioinformatics (INB), Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
Arcadi
A
Navarro
Department of Pathology and Experimental Therapeutics, University of Barcelona, L'Hospitalet de Llobregat, Spain.|Institute of Neuropathology, Service of Pathologic Anatomy, IDIBELL-Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Spain.|Institute of Neurosciences, University of Barcelona, Hospitalet de Llobregat, Spain.|CIBERNED, Network Centre for Biomedical Research of Neurodegenerative Diseases, Institute Carlos III, Spain.
Isidro
0000-0001-9888-8754
I
Ferrer
D005625:Frontal Lobe / Q000378:metabolism*; D020869:Gene Expression Profiling; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D006801:Humans; D020961:Lewy Body Disease / Q000235:genetics* / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
GABA; Lewy body diseases; axonema; cerebral cortex; chaperones; dementia with Lewy bodies; dynein; mitochondria; neurotransmission; purine metabolism; synapses; taste receptors; transcriptome