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Updated: Feb 16, 2026
Primary Cultures of Rat Astrocytes and Microglia and Their Use in the Study of Amyotrophic Lateral Sclerosis
Published on: June 23, 2022
Etiogenic factors present in the cerebrospinal fluid from amyotrophic lateral sclerosis patients induce predominantly
Pooja-Shree Mishra1,2, K Vijayalakshmi1, A Nalini3
1Department of Neurophysiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, 560029, India.
Background:
Microglial cell-associated neuroinflammation is considered as a potential contributor to the pathophysiology of sporadic amyotrophic lateral sclerosis. However, the specific role of microglia in the disease pathogenesis remains to be elucidated.
Methods:
We studied the activation profiles of the microglial cultures exposed to the cerebrospinal fluid from these patients which recapitulates the neurodegeneration seen in sporadic amyotrophic lateral sclerosis. This was done by investigating the morphological and functional changes including the expression levels of prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), TNF-α, IL-6, IFN-γ, IL-10, inducible nitric oxide synthase (iNOS), arginase, and trophic factors. We also studied the effect of chitotriosidase, the inflammatory protein found upregulated in the cerebrospinal fluid from amyotrophic lateral sclerosis patients, on these cultures.
Results:
We report that the cerebrospinal fluid from amyotrophic lateral sclerosis patients could induce an early and potent response in the form of microglial activation, skewed primarily towards a pro-inflammatory profile. It was seen in the form of upregulation of the pro-inflammatory cytokines and factors including IL-6, TNF-α, iNOS, COX-2, and PGE2. Concomitantly, a downregulation of beneficial trophic factors and anti-inflammatory markers including VEGF, glial cell line-derived neurotrophic factor, and IFN-γ was seen. In addition, chitotriosidase-1 appeared to act specifically via the microglial cells.
Conclusion:
Our findings demonstrate that the cerebrospinal fluid from amyotrophic lateral sclerosis patients holds enough cues to induce microglial inflammatory processes as an early event, which may contribute to the neurodegeneration seen in the sporadic amyotrophic lateral sclerosis. These findings highlight the dynamic role of microglial cells in the pathogenesis of the disease, thus suggesting the need for a multidimensional and temporally guarded therapeutic approach targeting the inflammatory pathways for its treatment.
Insights
Cerebrospinal fluid from amyotrophic lateral sclerosis patients triggers pro-inflammatory microglial activation, contributing to neurodegeneration. Targeting these inflammatory pathways is crucial for future ALS treatments.
Area of Science:
- Neuroscience
- Immunology
- Pathophysiology
Background:
- Microglial neuroinflammation is implicated in sporadic amyotrophic lateral sclerosis (ALS) pathogenesis.
- The precise role of microglia in ALS requires further investigation.
Purpose of the Study:
- To investigate microglial activation profiles in response to cerebrospinal fluid (CSF) from ALS patients.
- To elucidate the role of chitotriosidase in ALS-associated microglial activation.
Main Methods:
- Cultured microglia were exposed to ALS patient CSF.
- Morphological and functional changes were assessed, including cytokine and factor expression (PGE2, COX-2, TNF-α, IL-6, IFN-γ, IL-10, iNOS, arginase, VEGF, GDNF).
- The impact of chitotriosidase on microglial activation was evaluated.
Main Results:
- ALS CSF induced potent microglial activation, predominantly pro-inflammatory (upregulation of IL-6, TNF-α, iNOS, COX-2, PGE2).
- Beneficial trophic factors and anti-inflammatory markers (VEGF, GDNF, IFN-γ) were downregulated.
- Chitotriosidase-1 demonstrated specific action via microglial cells.
Conclusions:
- ALS patient CSF contains factors that initiate early microglial inflammatory responses, potentially driving neurodegeneration.
- Microglial cells play a dynamic role in ALS pathogenesis.
- Multidimensional, time-sensitive therapeutic strategies targeting inflammatory pathways are needed for ALS treatment.
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