Kinetics of creatine in blood and brain after intraperitoneal injection in the rat

Perasso, Luisa; Cupello, A.; Lunardi, G.; Principato, Cristina; Gandolfo, Carlo; Balestrino, Maurizio

doi:10.1016/s0006-8993(03)02547-2

Cited by 62 publications

(56 citation statements)

References 19 publications

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“…In vivo data confirmed this hypothesis: the blood to brain transport of Cr through BBB is effective in rats and mice but is relatively inefficient (Ohtsuki et al 2002;Perasso et al 2003), and long-term treatment of AGAT-and GAMT-deficient patients with high doses of Cr allows only a slow and in most cases partial replenishment of their brain Cr pools (Stöckler et al 2007;Schulze and Battini 2007). Similarly, GAMT -/-KO mice treated with high doses of Cr replenish their brain Cr, but only slowly (Kan et al 2007).…”

Section: Creatine In Cns: Endogenous Synthesis Versus Uptake From Permentioning

confidence: 67%

“…Organotypic rat cortical cultures, primary brain cell cultures (neuronal, glial or mixed) and neuroblastoma cell lines have a Cr transporter activity (Möller and Hamprecht 1989;Almeida et al 2006;. In vivo, mouse and rat CNS can take up Cr from the blood against its concentration gradient (Ohtsuki et al 2002;Perasso et al 2003). SLC6A8 is expressed throughout the main regions of adult mammalian brain (Schloss et al 1994;Happe and Murrin 1995;Braissant et al 2001b;Tachikawa et al 2008;Mak et al 2009).…”

Section: Agat Gamt and Slc6a8 In Cnsmentioning

confidence: 99%

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Creatine deficiency syndromes and the importance of creatine synthesis in the brain

et al. 2011

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Creatine deficiency syndromes, due to deficiencies in AGAT, GAMT (creatine synthesis pathway) or SLC6A8 (creatine transporter), lead to complete absence or very strong decrease of creatine in CNS as measured by magnetic resonance spectroscopy. Brain is the main organ affected in creatine-deficient patients, who show severe neurodevelopmental delay and present neurological symptoms in early infancy. AGAT-and GAMT-deficient patients can be treated by oral creatine supplementation which improves their neurological status, while this treatment is inefficient on SLC6A8-deficient patients. While it has long been thought that most, if not all, of brain creatine was of peripheral origin, the past years have brought evidence that creatine can cross blood-brain barrier, however, only with poor efficiency, and that CNS must ensure parts of its creatine needs by its own endogenous synthesis. Moreover, we showed very recently that in many brain structures, including cortex and basal ganglia, AGAT and GAMT, while found in every brain cell types, are not coexpressed but are rather expressed in a dissociated way. This suggests that to allow creatine synthesis in these structures, guanidinoacetate must be transported from AGAT-to GAMT-expressing cells, most probably through SLC6A8. This new understanding of creatine metabolism and transport in CNS will not only allow a better comprehension of brain consequences of creatine deficiency syndromes, but will also contribute to better decipher creatine roles in CNS, not only in energy as ATP regeneration and buffering, but also in its recently suggested functions as neurotransmitter or osmolyte.

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Section: Creatine In Cns: Endogenous Synthesis Versus Uptake From Permentioning

confidence: 67%

Section: Agat Gamt and Slc6a8 In Cnsmentioning

confidence: 99%

Creatine deficiency syndromes and the importance of creatine synthesis in the brain

et al. 2011

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“…In vivo experiments in mouse and rat have demonstrated that CNS can take up Cr from the blood against its concentration gradient, at least to some extent (Ohtsuki et al 2002;Perasso et al 2003). However, it has been known for a very long time that this passage of peripheral Cr into the brain is limited.…”

Section: Cr and Gaa Through Bbb And Bcsfb And Within Cnsmentioning

confidence: 99%

“…This raised the concept that BBB has a limited permeability for peripheral Cr, and that the brain supplies a part of its Cr by endogenous synthesis (Braissant et al 2001b;Braissant et al 2011;Braissant and Henry 2008). However, despite indeed a limited efficiency of brain Cr uptake from periphery, shown in vivo both in rodents (Ohtsuki et al 2002;Perasso et al 2003) as well as in AGAT-and GAMT-deficient patients (AGAT: OMIM #612718; GAMT: OMIM #612736) treated by Cr (Schulze 2005), Cr (and the intermediate guanidinoacetate, GAA) do cross BBB and BCSFB (Tachikawa and Hosoya 2011). This review brings together (i) the latest experimental data on the transport of Cr and GAA through BBB and BCSFB with (ii) the clinical evidence shown in the patients deficient for AGAT, GAMT and SLC6A8 (SLC6A8: OMIM #300352), in order to delineate a clearer view of the roles of BBB and BCSFB in the transport of Cr and GAA between periphery and CNS, and on the synthesis and transport of Cr within the brain, both in the mature brain and during development.…”

Section: Introductionmentioning

confidence: 99%

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

Braissant

2012

J of Inher Metab Disea

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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.

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“…The radioactive content was determined, 5min per sample, in a liquid scintillation counter (LS-6500, Beckman, USA), and the number of counts per minute detected in the plasma and in the brain tissue were expressed in nanomoles of 5-HT, based on the counts in the working solution of known concentration (N8). Times in the order of 10-15min are commonly used in studies of this type in mammals (Buschiazzo et al, 1970;Vitte et al, 1988;Naylor et al, 1995;Preston et al, 1995;Perasso et al, 2003) and fish . If a substance passes the BBB it will actually be detectable in the brain long before 15min.…”

Section: -Ht and The Blood-brain Barriermentioning

confidence: 99%

Homeostasis of glucose in the rainbow trout (Oncorhynchus mykiss Walbaum): the role of serotonin

Tubío

Maceira

Aldegunde

2010

Journal of Experimental Biology

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Kinetics of creatine in blood and brain after intraperitoneal injection in the rat

Cited by 62 publications

References 19 publications

Creatine deficiency syndromes and the importance of creatine synthesis in the brain

Creatine deficiency syndromes and the importance of creatine synthesis in the brain

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

Homeostasis of glucose in the rainbow trout (Oncorhynchus mykiss Walbaum): the role of serotonin

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