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Updated: Jun 21, 2025
Primary Cultures of Rat Astrocytes and Microglia and Their Use in the Study of Amyotrophic Lateral Sclerosis
Published on: June 23, 2022
Ferritin is closely associated with microglia in amyotrophic lateral sclerosis
Ju Gao1, Ogoegbunam Okolo2, Sandra L Siedlak2
1Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, United States.
Abstract:
Iron deposition is a hallmark of amyotrophic lateral sclerosis (ALS) and has been strongly implicated in its pathogenesis. As a byproduct of cellular oxidative stress, iron dysregulation modifies basal levels of the regulatory iron-binding protein ferritin. Examination of thoracic and lumbar spinal cord tissues found increased ferritin immunostaining in white matter axons that corresponded to areas of increased microgliosis in 8 ALS patients versus 8 normal subjects. Gray matter areas containing the motor neurons also demonstrated increased ferritin and microglia in ALS compared to controls but at lower levels than in the white matter. Motor neurons with or without TDP-43 inclusions did not demonstrate either increased ferritin or associated microglial activation. We also observed an association of ferritin with microglia in cerebral cortical tissue samples of ALS cases and in the spinal cord tissues of transgenic mice expressing the SOD1G93A mutation. Elevated ferritin levels were detected in the insoluble fraction from spinal cord tissues of individuals with ALS. These findings suggest that activated microglia and increased ferritin may play significant roles in ALS progression since they are found closely associated in areas of axonal and cortical degeneration.
Insights
Iron accumulation and increased ferritin, a protein that binds iron, are linked to amyotrophic lateral sclerosis (ALS) progression. These changes are associated with activated microglia in affected brain and spinal cord areas.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Iron deposition is a key feature of amyotrophic lateral sclerosis (ALS).
- Iron dysregulation affects ferritin levels, a key iron-binding protein.
- Oxidative stress contributes to iron dysregulation in ALS.
Purpose of the Study:
- To investigate the relationship between iron deposition, ferritin, and microglial activation in ALS.
- To examine ferritin and microglial changes in spinal cord and cerebral cortex tissues of ALS patients and a mouse model.
Main Methods:
- Immunohistochemical analysis of spinal cord and cerebral cortical tissues from ALS patients and control subjects.
- Examination of spinal cord tissues from SOD1G93A transgenic mice.
- Biochemical fractionation to analyze ferritin levels in insoluble protein fractions.
Main Results:
- Increased ferritin immunostaining and microgliosis were observed in white matter axons of ALS spinal cords.
- Gray matter motor neurons also showed increased ferritin and microglia, but to a lesser extent than white matter.
- Ferritin was associated with microglia in ALS cortical tissues and SOD1G93A mouse spinal cords.
- Elevated ferritin levels were found in the insoluble fraction of ALS spinal cord tissues.
Conclusions:
- Activated microglia and increased ferritin are closely associated in degenerating areas of the central nervous system in ALS.
- These findings suggest a significant role for ferritin and microglia in ALS pathogenesis and progression.
- Further research into iron regulation and microglial pathways may offer therapeutic targets for ALS.
