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Updated: Jul 16, 2025
Author Spotlight: Microglia Research on Spinal Cord Heterogeneity and Purification
Published on: September 22, 2023
Aging spinal cord microglia become phenotypically heterogeneous and preferentially target motor neurons and their
Ryan W Castro1, Mikayla C Lopes2, Lindsay M De Biase3
1Neuroscience Graduate Program, Brown University, Providence, Rhode Island, USA.
Abstract:
Microglia have been found to acquire unique region-dependent deleterious features with age and diseases that contribute to neuronal dysfunction and degeneration in the brain. However, it remains unknown whether microglia exhibit similar phenotypic heterogeneity in the spinal cord. Here, we performed a regional analysis of spinal cord microglia in 3-, 16-, 23-, and 30-month-old mice. Using light and electron microscopy, we discovered that spinal cord microglia acquire an increasingly activated phenotype during the course of aging regardless of regional location. However, aging causes microglia in the ventral but not dorsal horn to lose their spatial organization. Aged ventral horn microglia also aggregate around the somata of motor neurons and increase their contacts with motor synapses, which have been shown to be lost with age. These findings suggest that microglia may affect the ability of motor neurons to receive and relay motor commands during aging. To generate additional insights about aging spinal cord microglia, we performed RNA-sequencing on FACS-isolated microglia from 3-, 18-, 22-, and 29-month-old mice. We found that spinal cord microglia acquire a similar transcriptional identity as those in the brain during aging that includes altered expression of genes with roles in microglia-neuron interactions and inflammation. By 29 months of age, spinal cord microglia exhibit additional and unique transcriptional changes known and predicted to cause senescence and to alter lysosomal and ribosomal regulation. Altogether, this work provides the foundation to target microglia to ameliorate aged-related changes in the spinal cord, and particularly on the motor circuit.
Insights
Aging spinal cord microglia become activated and lose organization in the ventral horn, impacting motor neurons. Transcriptional analysis reveals brain-like and unique age-related changes, suggesting therapeutic targets for motor circuit aging.
Area of Science:
- Neuroscience
- Immunology
- Aging Research
Background:
- Microglia, the brain's immune cells, exhibit age-related detrimental changes impacting neuronal function.
- The regional heterogeneity and aging effects on spinal cord microglia remain largely unexplored.
Purpose of the Study:
- To investigate regional phenotypic and transcriptional changes in aging spinal cord microglia.
- To understand the impact of aging microglia on motor neuron circuits in the spinal cord.
Main Methods:
- Regional analysis of spinal cord microglia in mice of different ages (3-30 months) using light and electron microscopy.
- RNA sequencing of FACS-isolated microglia from aged mice (3-29 months).
Main Results:
- Spinal cord microglia show increased activation with age across all regions.
- Aging leads to loss of spatial organization and aggregation around motor neurons in the ventral horn.
- Transcriptional profiles of aged spinal cord microglia resemble brain microglia, with unique age-related alterations in senescence, lysosomal, and ribosomal pathways.
Conclusions:
- Aging induces significant regional and transcriptional changes in spinal cord microglia, particularly affecting the motor circuit.
- These findings highlight microglia as potential therapeutic targets to mitigate age-related spinal cord dysfunction and motor deficits.
