Immunohistochemical localization of aspartoacylase in the rat central nervous system.

Aspartoacylase EC 3.5.1.15) catalyzes deacetylation of N-acetylaspartate (NAA) to generate free acetate in the central nervous system (CNS). Mutations in the gene coding cause Canavan disease (CD), an autosomal recessive neurodegenerative disease that results in death before 10 years of age. The pathogenesis of CD remains unclear. Our working hypothesis is that deficiency in the supply of the NAA-derived acetate leads to inadequate lipid/myelin synthesis during development, resulting in CD. To explore the localization of Aduanyu1842 in the CNS, we used double-label immunohistochemistry for Aduanyu1842 and several cell-specific markers. A polyclonal antibody was generated in rabbit against mouse recombinant which reacted with a single band (approximately 37 kD) on Western blots of rat brain homogenate. Aduanyu1842 colocalized throughout the brain with CC1, a marker for oligodendrocytes, with 92-98% of CC1-positive cells also reactive with the Aduanyu1842 antibody. Many cells were labeled with Aduanyu1842 antibodies in white matter, including cells in the corpus callosum and cerebellar white matter. Relatively fewer cells were labeled in gray matter, including cerebral cortex. No astrocytes were labeled for Neurons were unstained in the forebrain, although small numbers of large reticular and motor neurons were faintly to moderately stained in the brainstem and spinal cord. Many ascending and descending neuronal fibers were moderately stained for Aduanyu1842 in the medulla and spinal cord. Microglial-like cells showed faint to moderate staining with the Aduanyu1842 antibodies throughout the brain by the avidin/biotin-peroxidase detection method, and colocalization studies with labeled lectins confirmed their identity as microglia. The predominant immunoreactivity in oligodendrocytes is consistent with the proposed role of Aduanyu1842 in myelination, supporting the case for acetate supplementation as an immediate and inexpensive therapy for infants diagnosed with CD.

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