Expression of arginase isozymes in mouse brain

The two forms of arginase (Al and All) in man, identical in enzymatic function, are encoded in separate genes and are expressed differentially in various tissues. Al is expressed predominantly in the liver cytosol and is thought to function primarily to detoxify ammonia as part of the urea cycle. All, in contrast, is predominantly mitochondrial, is more widely expressed, and is thought to function primarily to produce ornithine. Ornithine is a precursor in the synthesis of proline, glutamate, and polyamines. This study was undertaken to explore the cellular and regional distribution of Al and All expression in brain using in situ hybridization and immunohistochemistry. Al and All were detected only in neurons and not in glial cells. Al presented stronger expression than All, but All was generally coexpressed with Al in most cells studied. Expression was particularly high in the cerebral cortex, cerebellum, pons, medulla, and spinal cord neurons. Glutamic acid decarboxylase 65 and glutamic acid decarboxylase 67, postulated to be related to the risk of glutamate excitotoxic and/or gamma -aminobutyric acid inhibitoxic injury, were similarly ubiquitous in their expression and generally paralleled arginase expression patterns, especially in cerebral cortex, hippocampus, cerebellum, pons, medulla, and spinal cord. This study showed that Al is expressed in the mouse brain, and more strongly than All, and sheds light on the anatomic basis for the arginine --> omithine --> glutamate --> GABA pathway. (C) 2001 Wiley-Liss, Inc.