The creatine transporter mediates the uptake of creatine by brain tissue, but not the uptake of two creatine-derived compounds

Lunardi, G.; Parodi, Alessandro; Perasso, Luisa; Pohvozcheva, A. V.; Scarrone, S.; Adriano, Enrico; Florio, Tullio; Gandolfo, Carlo; Cupello, A.; Буров, С. В.; Balestrino, Maurizio

doi:10.1016/j.neuroscience.2006.06.058

Cited by 47 publications

(73 citation statements)

References 22 publications

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“…T 2 ͓͑Gd͔͒ ϭ 1/͑0.84 ϩ 0.006 ͓Gd͔͒ [6] DISCUSSION FLAIR images obtained after intravenous injection of a Gd-based contrast agent allow a better evaluation of intracranial meningeal disease, revealing at visual inspection a more conspicuous enhancement of involved meningeal layers, with respect to contrast-enhanced T 1 -weighted MRI (3,9). The clinical use of contrast-enhanced FLAIR images to detect BBB damage has already been described in patients with acute stroke, in which the BBB leakage detected with FLAIR images has been proposed as a marker for increased risk of hemorrhagic transformation (1).…”

Section: Resultsmentioning

confidence: 99%

In vitro investigation of poor cerebrospinal fluid suppression on fluid‐attenuated inversion recovery images in the presence of a gadolinium‐based contrast agent

Bonzano

Roccatagliata

Levréro

et al. 2008

Magnetic Resonance in Med

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Section: Resultsmentioning

confidence: 99%

In vitro investigation of poor cerebrospinal fluid suppression on fluid‐attenuated inversion recovery images in the presence of a gadolinium‐based contrast agent

Bonzano

Roccatagliata

Levréro

et al. 2008

Magnetic Resonance in Med

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“…In theory it might be improved by creatine-derived compounds that cross biological membranes in a transporter-independent way. We previously reported that phosphocreatine-Mgcomplex (acetate) may be one of such drugs [19]. In the experiments described in the present paper we investigated if phosphocreatine-Mg-complex (acetate) and other creatine-derived molecules are capable of reproducing known biological effects of creatine in an in vitro model of brain anoxia.…”

Section: Acsfmentioning

confidence: 95%

“…To functionally inactivate the creatine transporter we used methods, derived from the literature, that we described in our previous work [19]. Briefly, we functionally inactivated the creatine transporter with either one of the following treatments: (a) adding to the incubation medium 10 mM GPA or (b) replacing NaCl in the medium with an equimolar amount of Na-acetate to obtain an almost total chloride-free incubation.…”

Section: Inactivation Of Creatine Transporter In Brain Slicesmentioning

confidence: 99%

Protective Effects of Some Creatine Derivatives in Brain Tissue Anoxia

et al. 2007

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Some derivatives more lipophylic than creatine, thus theoretically being capable to better cross the blood-brain barrier, were studied for their protective effect in mouse hippocampal slices. We found that N-amidino-piperidine is harmful to brain tissue, and that phosphocreatine is ineffective. Creatine, creatine-Mg-complex (acetate) and phosphocreatine-Mg-complex (acetate) increased the latency to population spike disappearance during anoxia. Creatine and creatine-Mg-complex (acetate) also increased the latency of anoxic depolarization, while the delay induced by phosphocreatine-Mg-complex (acetate) was of borderline significance (P = 0.056). Phosphocreatine-Mg-complex (acetate) significantly reduced neuronal hyperexcitability during anoxia, an effect that no other compound (including creatine itself) showed. For all parameters except reduced hyperexcitability the effects statistically correlated with tissue levels of creatine or phosphocreatine. Summing up, exogenous phosphocreatine and N-amidino piperidine are not useful for brain protection, while chelates of both creatine and phosphocreatine do replicate some of the known protective effects of creatine. In addition, phosphocreatine-Mg-complex (acetate) also reduced neuronal hyperexcitability during anoxia.

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“…While some derivatives (e.g., Namidino-piperidine) were harmful, others (e.g., Cr-Mgcomplex acetate, PCr-Mg-complex acetate and Cr ethyl ester) showed interesting neuroprotective effects in hippocampal organotypic cultures (a model with disruption of BBB) (Perasso et al 2008;Adriano et al 2011). PCr-Mgcomplex acetate and another derivative, Cr benzyl ester, were also demonstrated to cross cell membranes without the help of the Cr transporter (Lunardi et al 2006). More interestingly, PCr-Mg-complex acetate and the very recently described creatinyl amino acids showed neuroprotective effects in vivo in rodents, thus suggesting a crossing of BBB (Burov et al 2011;Perasso et al 2009).…”

Section: Creatine Derivatives For a Better Crossing Of Bbb?mentioning

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 creatine transporter mediates the uptake of creatine by brain tissue, but not the uptake of two creatine-derived compounds

Cited by 47 publications

References 22 publications

In vitro investigation of poor cerebrospinal fluid suppression on fluid‐attenuated inversion recovery images in the presence of a gadolinium‐based contrast agent

In vitro investigation of poor cerebrospinal fluid suppression on fluid‐attenuated inversion recovery images in the presence of a gadolinium‐based contrast agent

Protective Effects of Some Creatine Derivatives in Brain Tissue Anoxia

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

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