Abstract
High-affinity uptake of glycine and glutamate modulates glutamatergic neurotransmission in gray matter. N-Methyl- d-aspartate (NMDA) receptors were recently described on white matter oligodendrocytes, therefore uptake of glutamate and glycine in white matter may also modulate NMDA receptor function. We found that glycine uptake in white structures of pig forebrain (corpus callosum, fimbria, subcortical pyramidal tracts, and occipital subcortical white matter) was similar to that in gray structures (frontal and temporal cortices and hippocampus), and that it was sensitive to sarcosine, a GLYT1 inhibitor (IC 50 15 μM). Glutamate uptake in white matter was ∼10% of that in gray; it was sensitive to dihydrokainate, an EAAT2 inhibitor. The levels of glycine and its precursor serine were similar in white and gray matter: approximately 2 and 1 nmol/mg tissue, respectively. The white matter level of glutamate was ∼7.6 nmol/mg tissue, or ∼74% of gray matter levels. The activity of serine hydroxymethyl transferase, which converts serine into glycine, was similar in white and gray matter (11–18 pmol/(mg tissue) min), whereas the white matter activity of phosphate-activated glutaminase, which converts glutamine into glutamate, was ∼100 pmol/(mg tissue) min, or ∼34% of gray matter activity. The white matter activity of glutamine synthetase, the glial enzyme that converts glutamate into glutamine, was 20–40 nmol/(mg tissue) min in neocortex and 5–6 nmol/(mg tissue) min in white matter. The data show that forebrain white matter is equipped to regulate extracellular levels of glycine and glutamate, functions that may modulate white matter NMDA receptor function.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.