title: Amyotrophic lateral sclerosis, gene deregulation in the anterior horn of the spinal cord and frontal cortex area 8: implications in frontotemporal lobar degeneration.
abstract: Transcriptome arrays identifies 747 genes differentially expressed in the anterior horn of the spinal cord and 2,300 genes differentially expressed in frontal cortex area 8 in a single group of typical sALS cases without frontotemporal dementia compared with age-matched controls. Main up-regulated clusters in the anterior horn are related to inflammation and apoptosis; down-regulated clusters are linked to axoneme structures and protein synthesis. In contrast, up-regulated gene clusters in frontal cortex area 8 involve neurotransmission, synaptic proteins and vesicle trafficking, whereas main down-regulated genes cluster into oligodendrocyte function and myelin-related proteins. RT-qPCR validates the expression of 58 of 66 assessed genes from different clusters. The present results: a. reveal regional differences in de-regulated gene expression between the anterior horn of the spinal cord and frontal cortex area 8 in the same individuals suffering from sALS; b. validate and extend our knowledge about the complexity of the inflammatory response in the anterior horn of the spinal cord; and c. identify for the first time extensive gene up-regulation of neurotransmission and synaptic-related genes, together with significant down-regulation of oligodendrocyte- and myelin-related genes, as important contributors to the pathogenesis of frontal cortex alterations in the sALS/frontotemporal lobar degeneration spectrum complex at stages with no apparent cognitive impairment.
authors.affiliation: Institute of Neuropathology, Pathologic Anatomy Service, Bellvitge University Hospital, IDIBELL, Hospitalet de Llobregat, Spain.
authors.forename: Pol
authors.initials: P
authors.lastname: Andrés-Benito
authors.affiliation: Institute of Neuropathology, Pathologic Anatomy Service, Bellvitge University Hospital, IDIBELL, Hospitalet de Llobregat, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Moreno
authors.affiliation: Institute of Neuropathology, Pathologic Anatomy Service, Bellvitge University Hospital, IDIBELL, Hospitalet de Llobregat, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Aso
authors.affiliation: Service of Neurology, Bellvitge University Hospital, Hospitalet de Llobregat, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Povedano
authors.affiliation: Institute of Neuropathology, Pathologic Anatomy Service, Bellvitge University Hospital, IDIBELL, Hospitalet de Llobregat, Spain.|Department of Pathology and Experimental Therapeutics, University of Barcelona, Spain.|Institute of Neurosciences, University of Barcelona, Barcelona, Spain.|Biomedical Network Research Center on Neurodegenerative Diseases (CIBERNED), Institute Carlos III, Hospitalet de Llobregat, Spain.
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D059467:Transcriptome
keywords: amyotrophic lateral sclerosis; excitotoxicity; frontal cortex; frontotemporal lobar degeneration; neuroinflammation; spinal cord