Mitochondrial β-Oxidation Enzymes Are Regionally Expressed in the Mouse Brain † 1856

Mitochondrial fatty acid β-oxidation produces acetyl-CoA that is utilized by the enzymes of the Kreb's cycle in the generation of NADH and FADH2. The enzymes involved in the β-oxidation of fatty acids are very active in the heart, skeletal muscle, small intestine, kidney and liver. Information is lacking about their expression in the brain. To answer this question, we generated rabbit antibodies specific for purified recombinant very long and long chain acyl-CoA dehydrogenases (VLCAD, LCAD), long and short chain 3-hydroxy-acyl-CoA dehydrogenases (LCHAD, SCHAD) and 3-ketoacyl-CoA thiolase. The specificity of each antibody was confirmed by Western blot, and immunocytochemistry was performed to detect the expression in the adult mouse brain. Only neurons and endothelial cells in the choroid plexus were labeled by all the antibodies. Glial cells were not immunoreactive. In the cerebellum, Purkinje neurons and basket and stellate cells in the molecular layer were heavily stained. Although granule cells were not stained, 'rosette-like' structures were observed in the neuropil surrounding these cells. A small number of large neurons was stained in cortical layers IV and V. In the hippocampus, Ca1 and Ca3 pyramidal neurons were intensely stained, but protein expression was not detected in adjacent interneurons. Granule neurons in the dentate gyrus and interneurons located in the stratum moleculare expressed all the enzymes for fatty acid β-oxidation. These results suggest that neurons in these brain areas have the enzymatic machinery necessary to metabolize fatty acids of all lengths and use them as an alternative source of acetyl-CoA molecules for the Kreb's cycle. It is also likely that the expression of these enzymes reflects the unique energy requirements of these neurons and possibly their selective susceptibility to ischemic/hypoxic insults.