Endogenous synthesis and transport of creatine in the rat brain: an in situ hybridization study

Creatine is synthesized from arginine by L-arginine:glycine amidinotransfer ase (AGAT) and S-adenosyl-L-methionine:N-guanidinoacetate methyltransferase (GAMT) and can be taken up by cells by creatine transporters (CRT). While creatine is mainly synthesized by the liver and the kidney, most of other t issues, including the brain, also express AGAT and GAMT. There is evidence that the permeability of the blood-brain barrier (BBB) for creatine is limi ted, suggesting that the brain is dependent on its own creatine synthesis. In order to better understand creatine synthesis and transport in the centr al nervous system (CNS), we studied the regional distribution of cells expr essing AGAT, GAMT and the creatine transporter CRT1 in the adult rat brain by non-radioisotopic in situ hybridization. AGAT and GAMT presented an ubiq uitous neuronal and glial expression, whereas CRT1 was present in neurons a nd oligodendrocytes throughout the brain, but not in astrocytes. This indic ates that all cells in the CNS can synthesize creatine from arginine. The a bsence of expression of CRT1 in astrocytes and particularly in those contac ting capillary endothelial cells (BBB) reinforces the idea that under norma l conditions the creatine used by the brain is synthesized mainly in the CN S. Furthermore, the expression of CRT1 by neurons and oligodendrocytes indi cates that creatine trafficking is possible in those brain areas of main cr eatine consumption. (C) 2001 Elsevier Science B.V. All rights reserved.