Aging spinal cord microglia become phenotypically heterogeneous and preferentially target motor neurons and their synapses.

Autor: Castro RW; Neuroscience Graduate Program, Brown University, Providence, Rhode Island, USA., Lopes MC; Molecular Biology, Cell Biology & Biochemistry Graduate Program, Brown University, Providence, Rhode Island, USA., De Biase LM; Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA., Valdez G; Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island, USA.; Center for Translational Neuroscience, Robert J. and Nancy D. Carney Institute for Brain Science, and Center on the Biology of Aging, Brown University, Providence, Rhode Island, USA.
Jazyk: angličtina
Zdroj: Glia [Glia] 2024 Jan; Vol. 72 (1), pp. 206-221. Date of Electronic Publication: 2023 Sep 22.
DOI: 10.1002/glia.24470
Abstrakt: 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.
(© 2023 Wiley Periodicals LLC.)
Databáze: MEDLINE
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