Journal of Inherited Metabolic Disease

, Volume 35, Issue 4, pp 655–664

Creatine and guanidinoacetate transport at blood-brain and blood-cerebrospinal fluid barriers

SSIEM Symposium 2011

DOI: 10.1007/s10545-011-9433-2

Cite this article as:
Braissant, O. J Inherit Metab Dis (2012) 35: 655. doi:10.1007/s10545-011-9433-2


While it was thought that most of cerebral creatine is of peripheral origin, AGAT and GAMT are well expressed in CNS where brain cells synthesize creatine. While the creatine transporter SLC6A8 is expressed by microcapillary endothelial cells (MCEC) at blood-brain barrier (BBB), it is absent from their surrounding astrocytes. This raised the concept that BBB has a limited permeability for peripheral creatine, and that the brain supplies a part of its creatine by endogenous synthesis. This review brings together the latest data on creatine and guanidinoacetate transport through BBB and blood-CSF barrier (BCSFB) with the clinical evidence of AGAT-, GAMT- and SLC6A8-deficient patients, in order to delineate a clearer view on the roles of BBB and BCSFB in the transport of creatine and guanidinoacetate between periphery and CNS, and on brain synthesis and transport of creatine. It shows that in physiological conditions, creatine is taken up by CNS from periphery through SLC6A8 at BBB, but in limited amounts, and that CNS also needs its own creatine synthesis. No uptake of guanidinoacetate from periphery occurs at BBB except under GAMT deficiency, but a net exit of guanidinoacetate seems to occur from CSF to blood at BCSFB, predominantly through the taurine transporter TauT.

Copyright information

© SSIEM and Springer 2012

Authors and Affiliations

  1. 1.Inborn Errors of Metabolism, Service of BiomedicineLausanne University HospitalLausanneSwitzerland