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Extensive aspartoacylase expression in the rat central nervous system
John R Moffett1, Peethambaran Arun, Prasanth S Ariyannur
1Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA. jmoffett@usuhs.mil
Glia
|May 21, 2011
Summary
Aspartoacylase (ASPA) is crucial for brain development, as mutations cause Canavan disease. This study maps ASPA expression in adult rat CNS, revealing its presence in oligodendrocytes, microglia, and neurons, suggesting roles in myelination and lipid synthesis.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Aspartoacylase (ASPA) enzyme deacetylates N-acetylaspartate (NAA) to acetate and aspartate.
- ASPA deficiency leads to Canavan disease, a fatal leukodystrophy due to reduced CNS acetate during development.
- Understanding ASPA expression is vital for insights into normal brain function and disease pathogenesis.
Purpose of the Study:
- To investigate the central nervous system (CNS) expression pattern of Aspartoacylase (ASPA) in adult rats.
- To identify specific cell types and locations of ASPA immunoreactivity within the CNS.
- To correlate ASPA expression with potential functions in myelination, lipid synthesis, and nuclear acetylation.
Main Methods:
- Utilized highly specific polyclonal antibodies against ASPA for immunohistochemical analysis in adult rat CNS tissue.
- Examined ASPA distribution in white matter, gray matter, microglia, ependymal cells, endothelial cells, and neuronal structures.
- Compared ASPA immunoreactivity with myelin basic protein and oligodendrocyte specific protein.
- Analyzed brain sections from tremor rats (ASPA-null mutant) as a negative control.
Main Results:
- ASPA was localized to oligodendrocyte cell bodies and nuclei in white matter, with a distribution distinct from myelin markers.
- Significant ASPA expression was observed in microglia, ependymal cells, pial cells, choroid plexus cells, and unidentified nuclear structures.
- Neuronal fibers (axoplasm) and some neurons, particularly in the brainstem and spinal cord, showed ASPA immunoreactivity.
- ASPA-immunoreactive elements were absent in tremor rats, confirming antibody specificity.
- Acetyl coenzyme A synthase immunoreactivity overlapped with ASPA in some axonal pathways.
Conclusions:
- ASPA expression in oligodendrocytes suggests a role in lipogenesis and myelination.
- Nuclear ASPA localization indicates a potential function in nuclear acetylation reactions, including histone acetylation.
- Microglial ASPA expression may be linked to lipid synthesis in these cells.
- Neuronal expression suggests some neurons possess the capacity for both NAA synthesis and catabolism.
- Findings provide a comprehensive map of ASPA distribution, supporting its multifaceted roles in the CNS.
