Send to

Choose Destination
Glia. 2011 Oct;59(10):1435-46. doi: 10.1002/glia.21187. Epub 2011 May 23.

Endogenous aspartoacylase expression is responsive to glutamatergic activity in vitro and in vivo.

Author information

Cell and Gene Therapy Center, UMDNJ School of Osteopathic Medicine, Stratford, New Jersey, USA.


Aspartoacylase (ASPA) is an enzyme that functions to catabolize the neuronal amino acid derivative N-acetyl-L-aspartic acid (NAA). Loss of this function results in the failure of developmental myelination. NAA synthesis and catabolism are tightly compartmentalized within neurons and oligodendrocytes, respectively, and there is evidence to suggest the developmental regulation of ASPA activity is transcriptional. NAA has no known direct physiological mode of action, and the identification of a transcriptional regulator of aspa would provide an opportunity to link NAA to relatively more characterized physiological contexts with a view to definitive functional classification. Using transcriptional and immunohistochemical endpoints, we define a window of postnatal development punctuated by increases in aspa within a pre-existing population of oligodendrocytes in the rat brain. Ontological mining of expression data generated in aspa-null rats during this developmental window identifies both neuronal and oligodendroglial transcriptional abnormalities that suggest an association between glutamatergic synaptic activity and ASPA. Glutamate, but not NAA, is shown to activate endogenous aspa expression in vitro, and endogenous aspa expression is upregulated in the brains of animals over expressing vesicular glutamate transporter type-I (vglut1). These results define a discrete period of postnatal development within which glutamate provides a means by which the tightly compartmentalized NAA metabolic cycle can function in sync with normal development and may be a factor in pathological models of dysregulated NAA metabolism.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center