Immunocytochemical localization of acyl-CoA oxidase in the rat central nervous system

Peroxisomal beta -oxidation, consisting of four steps catalysed by an acyl- CoA oxidase, a multifunctional protein and a thiolase, is responsible for t he shortening of a variety of lipid compounds. The first reaction of this p athway is catalysed by a FAD-containing acyl-CoA oxidase, three isotypes of which have been so far recognised. Among these, straight-chain acyl-CoA ox idase (ACOX) acts on long and very long chain fatty acids, prostaglandins a nd some xenobiotics. We investigated ACOX localisation by means of a sensit ive, tyramide based, immunocytochemical technique, thus obtaining a complet e distribution atlas of the enzyme in adult rat CNS. Granular immunoreactio n product was found in the cytoplasm of neuronal and glial cells, both in t he perikarya and in the cell processes. ACOX immunoreactive neurons were pr esent to variable extent, in either forebrain or hindbrain areas. Specifica lly, the strongest signal was detected in the pallidum, septum, red nucleus , reticular formation, nuclei of the cranial nerves, and motoneurons of the spinal cord. We then compared the ACOX immunoreactivity pattern with our p revious distribution maps of other peroxisomal enzymes in the adult rat bra in. While ACOX appeared to colocalise with catalase in the majority of cere bral regions, some differences with respect to d-amino acid oxidase were no ted. These observations support the hypothesis of heterogeneous peroxisomal populations in the nervous tissue. The wide distribution of the enzyme in the brain is consistent with the severe and generalised neurological altera tions characterising the peroxisomal disorder caused by ACOX deficiency (ps eudo-neonatal adrenoleukodystrophy).