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Updated: Jul 4, 2025
Primary Cultures of Rat Astrocytes and Microglia and Their Use in the Study of Amyotrophic Lateral Sclerosis
Published on: June 23, 2022
Genetic background variation impacts microglial heterogeneity and disease progression in amyotrophic lateral
Okiru Komine1,2, Syuhei Ohnuma1,2, Kunihiko Hinohara3,4,5
1Department of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi, Japan.
Abstract:
Recent single-cell analyses have revealed the complexity of microglial heterogeneity in brain development, aging, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Disease-associated microglia (DAMs) have been identified in ALS mice model, but their role in ALS pathology remains unclear. The effect of genetic background variations on microglial heterogeneity and functions remains unknown. Herein, we established and analyzed two mice models of ALS with distinct genetic backgrounds of C57BL/6 and BALB/c. We observed that the change in genetic background from C57BL/6 to BALB/c affected microglial heterogeneity and ALS pathology and its progression, likely due to the defective induction of neurotrophic factor-secreting DAMs and impaired microglial survival. Single-cell analyses of ALS mice revealed new markers for each microglial subtype and a possible association between microglial heterogeneity and systemic immune environments. Thus, we highlighted the role of microglia in ALS pathology and importance of genetic background variations in modulating microglial functions.
Insights
Genetic background significantly impacts microglial heterogeneity and amyotrophic lateral sclerosis (ALS) progression. Different mouse models reveal how variations affect disease-associated microglia (DAMs) and neuroinflammation.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Single-cell analyses reveal microglial heterogeneity in brain development, aging, and neurodegenerative diseases like ALS.
- Disease-associated microglia (DAMs) are implicated in ALS, but their precise role and the influence of genetic background are unclear.
Purpose of the Study:
- To investigate how distinct genetic backgrounds (C57BL/6 vs. BALB/c) affect microglial heterogeneity and ALS pathology.
- To identify new markers for microglial subtypes and understand their association with systemic immune environments in ALS.
Main Methods:
- Establishment and analysis of two ALS mouse models with different genetic backgrounds.
- Application of single-cell analyses to characterize microglial populations and their functions.
- Comparative analysis of ALS pathology and progression between the two mouse models.
Main Results:
- Genetic background significantly altered microglial heterogeneity and ALS pathology progression.
- The BALB/c background impaired neurotrophic factor-secreting DAM induction and microglial survival compared to C57BL/6.
- Single-cell data identified novel markers for microglial subtypes and suggested links between microglial diversity and systemic immunity.
Conclusions:
- Microglia play a crucial role in ALS pathology.
- Genetic background variations critically modulate microglial functions and influence ALS disease progression.
- Understanding microglial heterogeneity in different genetic contexts is vital for ALS research.
