Complex Inflammation mRNA-Related Response in ALS Is Region Dependent.

Sara Berjaoui,Margarita Carmona,Ester Aso,Mónica Povedano,Isidre Ferrer,Paula Garcia-Esparcia

doi:10.1155/2015/573784

Abstract

Inflammatory changes are analyzed in the anterior spinal cord and frontal cortex area 8 in typical spinal-predominant ALS cases. Increased numbers of astrocytes and activated microglia are found in the anterior horn of the spinal cord and pyramidal tracts. Significant increased expression of TLR7, CTSS, and CTSC mRNA and a trend to increased expression of IL10RA, TGFB1, and TGFB2 are found in the anterior lumbar spinal cord in ALS cases compared to control cases, whereas C1QTNF7 and TNFRSF1A mRNA expression levels are significantly decreased. IL6 is significantly upregulated and IL1B shows a nonsignificant increased expression in frontal cortex area 8 in ALS cases. IL-6 immunoreactivity is found in scattered monocyte-derived macrophages/microglia and TNF-α in a few cells of unknown origin in ALS cases. Increased expression and abnormal distribution of IL-1β occurred in motor neurons of the lumbar spinal cord in ALS. Strong IL-10 immunoreactivity colocalizes with TDP-43-positive inclusions in motor neurons in ALS cases. The present observations show a complex participation of cytokines and mediators of the inflammatory response in ALS consistent with increased proinflammatory cytokines and sequestration of anti-inflammatory IL-10 in affected neurons.

Highlights

Amyotrophic lateral sclerosis (ALS) is a progressive agedependent neurodegenerative disease with an estimated incidence of about 1–3/100,000 resulting in death on average within 3–5 years of symptom onset
Neuropathological examination in all cases was routinely performed on twenty selected dewaxed paraffin sections comprising different regions of the cerebral cortex, diencephalon, thalamus, brain stem, and cerebellum and several levels of the spinal cord, which were stained with haematoxylin and eosin, Kluver-Barrera, and, for immunohistochemistry to microglia, glial fibrillary acidic protein, βamyloid, phosphorylated tau, α-synuclein, TDP43, ubiquitin, and p62
The present findings demonstrate intrinsic regulation of cytokines and mediators of the immune response in the anterior part of the lumbar spinal cord and frontal cortex area 8 in ALS cases compared to agematched controls

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is a progressive agedependent neurodegenerative disease with an estimated incidence of about 1–3/100,000 resulting in death on average within 3–5 years of symptom onset. ALS is not a rare disease with lifetime risk of 1 : 1000 and 2 : 1 male predominance. ALS is primarily a motor neuron disease affecting the upper (cortical) and lower (brain stem and spinal) motor neurons with concomitant muscle atrophy, a proportion of patients develop frontotemporal lobar degeneration and occasionally other neurological symptoms. ALS is a multisystem degeneration with predominant motor symptoms. About 8–10% of cases are inherited (fALS), the majority of them autosomal dominant but some of them recessive or X-linked. The cause of ALS in the majority of sporadic cases is not known

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