Complex Inflammation mRNA-Related Response in ALS Is Region Dependent
Sara Berjaoui1, Mónica Povedano2, Paula Garcia-Esparcia1
1Institute of Neuropathology, Bellvitge University Hospital, University of Barcelona, CIBERNED (Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas), 08907 L'Hospitalet de Llobregat, Spain.
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.
Insights
This study reveals significant inflammatory changes in the spinal cord and brain of Amyotrophic Lateral Sclerosis (ALS) patients. Pro-inflammatory cytokines are elevated, while anti-inflammatory signals are sequestered within neurons.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease.
- Neuroinflammation plays a critical role in ALS pathogenesis.
- Understanding inflammatory mediators is key to developing therapeutic strategies.
Purpose of the Study:
- To investigate inflammatory changes in the spinal cord and frontal cortex of ALS patients.
- To analyze the expression of specific cytokines and inflammatory markers.
- To correlate inflammatory profiles with disease characteristics.
Main Methods:
- Analysis of inflammatory markers in post-mortem spinal cord and frontal cortex tissue.
- Quantitative assessment of astrocyte and microglia activation.
- Measurement of mRNA and protein expression of key cytokines and receptors (e.g., TLR7, IL-6, IL-1β, IL-10).
Main Results:
- Increased astrocytes and activated microglia in the spinal cord anterior horn and pyramidal tracts.
- Differential mRNA expression of inflammatory genes (TLR7, CTSS, CTSC upregulated; C1QTNF7, TNFRSF1A downregulated) in the ALS spinal cord.
- Upregulation of IL-6 and IL-1β in the ALS frontal cortex.
- IL-10 immunoreactivity colocalized with TDP-43 inclusions in motor neurons.
Conclusions:
- ALS involves complex inflammatory responses with both pro- and anti-inflammatory mediator involvement.
- Elevated pro-inflammatory cytokines and sequestered anti-inflammatory IL-10 in neurons contribute to ALS pathology.
- These findings highlight the intricate role of neuroinflammation in ALS progression.
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