Increased N-acetylaspartate in model mouse of Pelizaeus-Merzbacher disease.

Abstract

PURPOSE: To evaluate the N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) biochemical pathways in the brain of myelin synthesis-deficient (msd) mouse, a model of Pelizaeus-Merzbacher disease (PMD). MATERIALS AND METHODS: We performed magnetic resonance imaging and proton magnetic resonance spectroscopy (¹H-MRS) of the thalamus for msd and wildtype mice with a 7.0 T magnet. NAA and NAAG were independently measured by high-performance liquid chromatography (HPLC). Immunohistochemical analysis using anti-Mbp, Gfap, Ng2, and NeuN antibodies were also performed. RESULTS: ¹H-MRS in msd mice revealed increased total NAA (tNAA, NAAþNAAG), creatine, glutamine, and glutamate and decreased choline (Cho). HPLC analysis revealed increases of both NAA and NAAG in the msd brains. Histologically, the msd brains revealed hypomyelination and astrogliosis. Oligodendrocyte progenitor cells and neurons were normal in number in the thalamus wherein ¹H-MRS was obtained. CONCLUSION: The evidence suggests that the neurochemical derangement in the msd mice may be a primary increase of NAA resulting in a secondary increase of NAAG. Increased tNAA with decreased Cho detectable on ¹H-MRS may be an important marker for PMD, and might be used to distinguish it from more common neurological disorders that have decreased tNAA.