Evidence for glutamine synthetase function in mouse spinal cord oligodendrocytes

Glia, 2021 · DOI: 10.1002/glia.24071 · Published: December 1, 2021

Simple Explanation

Glutamine synthetase (GS) is an enzyme that converts glutamate into glutamine. It's mostly known to be in astrocytes, a type of brain cell, but this study found it in other brain cells as well. The researchers discovered GS in oligodendrocytes (OL), which are cells that make myelin, a coating that helps nerves transmit signals quickly. They looked at both mouse and human spinal cords. When they removed GS from OL in mice, the mice had a temporary decrease in their peak strength. GS expression was also increased in OL in models of ALS and multiple sclerosis, suggesting GS plays a role in these diseases.

Study Duration

Not specified

Participants

Mice (various strains including reporter and cKO lines), human spinal cord samples

Evidence Level

Level 3; Experimental study using reporter mice, cKO mice, human tissue, scRNA-seq data.

Key Findings

1
GS is expressed in myelinating oligodendrocytes (OL) but not oligodendrocyte progenitor cells in the mouse and human ventral spinal cord.
2
Conditional knockout of GS in OL leads to a significant decrease in glutamine levels in spinal cord extracts.
3
GS cKO mice showed a transient and specific decrease in peak force.

Research Summary

The study investigates the expression and function of glutamine synthetase (GS) in oligodendrocytes (OL) of the mouse and human spinal cord. The researchers found that GS is expressed in mature OL but not in oligodendrocyte progenitor cells (OPCs). OL-specific knockout of GS resulted in a transient decrease in peak force in mice, and GS expression in OL was found to be dysregulated in models of ALS and multiple sclerosis.

Practical Implications

Sensorimotor Axis Function

OL-encoded GS functions in the spinal cord sensorimotor axis, contributing to peak strength.

Neurological Disease Mechanisms

GS dysregulation in OL could impact neuron-glia crosstalk and contribute to Glu-mediated pathological mechanisms in diseases like ALS and MS.

Therapeutic Targets

Targeting GS in OL might offer potential therapeutic strategies for neurological disorders.

Study Limitations

1
Histological approaches may not be sensitive enough to detect subtle changes in motor neuron function.
2
The study did not investigate the electrophysiological properties of motor neurons in GS cKO mice.
3
The behavioral effect could result from cumulative effects of GS loss of function in both the CNS and PNS.

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