Research Paper Volume 9, Issue 3 pp 823—851
Amyotrophic lateral sclerosis, gene deregulation in the anterior horn of the spinal cord and frontal cortex area 8: implications in frontotemporal lobar degeneration
- 1 Institute of Neuropathology, Pathologic Anatomy Service, Bellvitge University Hospital, IDIBELL, Hospitalet de Llobregat, Spain
- 2 Service of Neurology, Bellvitge University Hospital, Hospitalet de Llobregat, Spain
- 3 Department of Pathology and Experimental Therapeutics, University of Barcelona, Spain
- 4 Institute of Neurosciences, University of Barcelona, Barcelona, Spain
- 5 Biomedical Network Research Center on Neurodegenerative Diseases (CIBERNED), Institute Carlos III, Hospitalet de Llobregat, Spain
Received: November 17, 2016 Accepted: February 27, 2017 Published: March 9, 2017
https://doi.org/10.18632/aging.101195How to Cite
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.