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

Pol Andrés-Benito¹, Jesús Moreno¹, Ester Aso¹, Mónica Povedano², Isidre Ferrer^1,^3,^4,⁵

¹Institute of Neuropathology, Pathologic Anatomy Service, Bellvitge University Hospital, IDIBELL, Hospitalet de Llobregat, Spain
²Service of Neurology, Bellvitge University Hospital, Hospitalet de Llobregat, Spain
³Department of Pathology and Experimental Therapeutics, University of Barcelona, Spain
⁴Institute of Neurosciences, University of Barcelona, Barcelona, Spain
⁵Biomedical Network Research Center on Neurodegenerative Diseases (CIBERNED), Institute Carlos III, Hospitalet de Llobregat, Spain

Received: November 17, 2016Accepted: February 27, 2017Published: March 9, 2017

Copyright: © 2017 Andrés-Benito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.