Specific alterations in the levels of N-acetyl-aspartyl-glutamate in the nervous system of the dystrophic mouse

Abstract

Determinations of N-acetyl-aspartate (NAA) and N-acetyl-aspartyl-glutamate (NAAG) levels were obtained by ion-exchange HPLC from 10 regions of the male dystrophic mouse brain as well as from those of non-dystrophic littermate controls. Similar to previous studies in the rat, NAA levels in control mice were distributed rather uniformly while NAAG levels exhibited a pronounced rostrocaudal gradient, with highest levels found in the lumbar spinal cord. Contrary to a recent report, we found no significant alterations in gross brain or spinal cord levels of NAA. In contrast, levels of NAAG were substantially and differentially reduced in several regions of the dystrophic mouse nervous system. These results demonstrate a pathological dissociation between NAA and NAAG, whose levels are known to display differential regional, ontogenetic and phylogenetic patterns. In addition, they may represent an ability of neural tissue to differentially regulate their steady-state levels, if indeed they can be shown to be biosynthetically related. The pronounced and non-uniform NAAG reductions observed in the dystrophic CNS underscores recent suggestions of a role for the neuropeptide in central systems involved in the control of motor function.