Oligodendrocytes Do Not Export NAA-Derived Aspartate In Vitro

Area of Science:

• Neuroscience
• Cellular Metabolism
• Oligodendrocyte Biology

Background:

• Oligodendrocytes deacetylate neuronal N-acetylaspartate (NAA) for lipid synthesis.
• The intermediary metabolism of NAA-derived aspartate in oligodendrocytes is poorly understood.
• Two hypotheses exist: aspartate metabolism in mitochondria or release into the medium.

Purpose of the Study:

• To investigate the metabolic fate of aspartate derived from N-acetylaspartate (NAA) in differentiating oligodendrocytes.
• To determine if aspartate enters mitochondrial metabolism or is released by these cells.
• To elucidate the role of NAA catabolism in oligodendrocyte intermediary metabolism.

Main Methods:

• Cultured primary rat oligodendrocyte progenitor cells (OPCs) were differentiated.
• Metabolic analysis using isotope-labeled [1,6-¹³C]glucose.
• Gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) of cell extracts and media.

Main Results:

• Aspartoacylase mRNA expression increased during OPC differentiation.
• The acetate moiety from NAA hydrolysis does not enter mitochondrial metabolism as acetyl-CoA.
• Aspartate is not significantly released into the medium by mature oligodendrocytes.

Conclusions:

• Aspartate derived from NAA rapidly joins the cytosolic aspartate pool in oligodendrocytes.
• This aspartate participates in the malate-aspartate shuttle for transporting reducing equivalents.
• Aspartate enters the tricarboxylic acid cycle at a slow rate, supporting oligodendrocyte metabolism.