Evidence for glutamine synthetase function in mouse spinal cord oligodendrocytes

Area of Science:

• Neuroscience
• Glial Biology
• Enzymology

Background:

• Glutamine synthetase (GS) is crucial for glutamate-glutamine metabolism, primarily in astrocytes.
• GS expression has been observed in other glial cells, prompting investigation into its role beyond astrocytes.

Purpose of the Study:

• To determine if GS is expressed in oligodendrocytes (OL) and investigate its function in mature OL.
• To explore the role of OL-specific GS in spinal cord sensorimotor function and its relevance in neurological diseases.

Main Methods:

• Utilized reporter mice and cell type-specific markers to identify GS expression in mouse and human ventral spinal cord.
• Generated conditional knockout (cKO) mice (CNP-cre+:Glulfl/fl) to selectively delete the Glul gene in OL.
• Analyzed spinal cord extracts for glutamine levels, assessed motor neuron integrity, OL differentiation, myelination, and motor performance.

Main Results:

• GS is expressed in myelinating OL but not oligodendrocyte progenitor cells in the ventral spinal cord.
• Selective deletion of Glul in OL led to decreased glutamine levels but did not affect motor neuron counts, OL differentiation, or myelination.
• GS cKO mice exhibited a transient decrease in peak force, with no impact on locomotion or motor coordination.
• OL-specific GS expression increased in SOD1(G93A) mice with amyotrophic lateral sclerosis and in human multiple sclerosis tissues.

Conclusions:

• Oligodendrocyte-derived GS plays a role in the spinal cord sensorimotor axis.
• Dysregulation of OL-specific GS occurs in chronic neurological conditions like ALS and MS.
• GS in OL represents a potential therapeutic target for neurological diseases.