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Updated: Dec 14, 2025
Primary Cultures of Rat Astrocytes and Microglia and Their Use in the Study of Amyotrophic Lateral Sclerosis
Published on: June 23, 2022
Motor cortex transcriptome reveals microglial key events in amyotrophic lateral sclerosis
Oriol Dols-Icardo1, Víctor Montal2, Sònia Sirisi2
1From the Memory Unit (O.D.-I., V.M., S.S., G.L.-P., L.C.-C., M.Q.-V., L.M., O.B., D.A., J.P., R.B., A.L., J.F., J.C.), Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED) (O.D.-I., V.M., S.S., G.L.-P., L.C.-C., M.Q.-V., L.M., O.B., D.A., J.P., R.B., A.L., J.F., J.C.), Madrid; Neurological Tissue Bank of the Biobanc-Hospital Clínic-IDIBAPS (L.M.-P.), Barcelona; Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department (L.M.-P.), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona; Network Center for Biomedical Research in Rare Diseases (CIBERER) (J.T.-S., R.R.-G.), Madrid; and Neuromuscular Disorders Unit (J.T.-S., R.R.-G.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain. jclarimon@santpau.cat odols@santpau.cat.
Disease-associated microglia (DAM) drive neuroinflammation in the motor cortex of amyotrophic lateral sclerosis (ALS) patients, alongside reduced synaptic gene expression.
Area of Science:
- Neuroscience
- Genomics
- Pathology
Background:
- Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease.
- Understanding molecular and cellular changes in the motor cortex is crucial for ALS research.
Purpose of the Study:
- To investigate transcriptomic alterations, neuropathologic features, and cellular changes in the motor cortex of sporadic ALS patients.
- To identify specific cell subpopulations involved in ALS pathogenesis.
Main Methods:
- Massive RNA sequencing of motor cortex tissue from ALS patients and healthy controls.
- Analysis of gene expression, isoform usage, and coexpression networks.
- Cell type deconvolution using single-nucleus RNA sequencing data and immunohistochemistry.
Main Results:
- Extensive RNA expression changes were observed, particularly in neuroinflammatory and synaptic pathways.
- An overrepresentation of microglial cells, specifically disease-associated microglia (DAM), was identified in ALS.
- pTDP43 aggregate density correlated negatively with microglial cell proportion.
Conclusions:
- Disease-associated microglia (DAM) play a key role in motor cortex neuroinflammation in ALS.
- ALS is associated with reduced expression of postsynaptic transcripts.
