In situ hybridization analysis of CHOT1, a creatine transporter, in the rat central nervous system

Hk, Happe; Lc, Murrin

doi:10.1002/cne.903510109

Cited by 47 publications

(34 citation statements)

References 35 publications

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“…The in vitro measurements of CK isoenzymes and CrT and the in vivo CK-catalyzed reaction rate constants in the developing rabbit cerebral gray matter and white matter allow a direct comparison to the recently published 31 P NMR measurements of the CK reactants PCr and ATP in these regions [15]. As previously seen in the rat, the relative ratio of Mi-CK to B-CK in gray matter is much higher than in white matter [4].…”

Section: Discussionmentioning

confidence: 54%

“…The CK-catalyzed reaction rate constants measured in vivo by 31 P NMR also showed regional differences in control and in Cr-treated rabbits (fig. 4, table 2).…”

Section: Resultsmentioning

confidence: 99%

“…These hypoxia-induced seizures are blocked by Cr with an associated increase in PCr/NTP ratio in both species. In the rabbit, the in vivo 31 P nuclear magnetic resonance (NMR) PCr signal first appears in white matter, but reaches mature levels at an earlier age in gray matter. Injecting Cr to rabbit pups at ages between 5 and 30 days increases PCr to adult levels in white matter and above adult levels in gray matter [15].…”

Section: Introductionmentioning

confidence: 99%

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Brain Creatine Kinase and Creatine Transporter Proteins in Normal and Creatine-Treated Rabbit Pups

Kekelidze

Khait²,

Togliatti³

et al. 2000

Dev Neurosci

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Systemic creatine (Cr) supplementation increases brain phosphocreatine (PCr) and prevents hypoxic seizures in 15-day-old rabbits . Between 5 and 30 days of age during normal development, rabbit gray matter mitochondrial creatine kinase (Mi-CK) increases 400% while cytosolic CK (BB-CK) increases 60%. In white matter, both isoenzymes show smaller, similar increases (40%) during this period. The Cr transporter protein decreases 60% between 5 and 15 days in both regions. In vivo CK rate constants measured by ³¹P nuclear magnetic resonance increase 30% between 10 and 20 days, and then fall 50% between 20 and 30 days in predominantly gray matter slices. Similar maturational changes are seen in predominantly white matter slices. Injecting Cr at 15 days does not significantly change BB-CK or Mi-CK isoenzymes or the in vivo CK reaction rate constants. Thus, the largest change in the CK system associated with suppression of hypoxic seizures in Cr-treated rabbits is increased PCr in gray and white matter.

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Section: Discussionmentioning

confidence: 54%

“…The CK-catalyzed reaction rate constants measured in vivo by 31 P NMR also showed regional differences in control and in Cr-treated rabbits (fig. 4, table 2).…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Brain Creatine Kinase and Creatine Transporter Proteins in Normal and Creatine-Treated Rabbit Pups

Kekelidze

Khait²,

Togliatti³

et al. 2000

Dev Neurosci

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“…One may speculate that the need for large numbers of astrocytes may be caused by the high energy demand of hippocampal pyramidal neurons, which have a higher synaptic density per neuron than other neocortical neurons (19). It is also supported by high amounts of cytosolic or mitochondrial creatine kinase isoenzymes found in granular and pyramidal cell layers of the hippocampus during postnatal development of rats as well as by high levels of expression of the creatine transporter in the pyramidal cell layer of adult rat brains (20,21). In humans, there is even evidence of muscle-type creatine kinase in pyramidal cells of the hippocampus proper (22).…”

Section: Discussionmentioning

confidence: 99%

Localized proton MRS of the human hippocampus: Metabolite concentrations and relaxation times

Choi

Frahm

1999

Magn. Reson. Med.

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Absolute concentrations and proton relaxation times of major metabolites in the human hippocampus were determined with use of fully relaxed, short-echo time STEAM localization sequences at 2.0 T (20 normal adults). Mean metabolite concentrations were 7.6 ؎ 0.9 mM for total N-acetylaspartate (tNAA), 6.9 ؎ 0.8 mM for total creatine (tCr), 2.1 ؎ 0.3 mM for cholinecontaining compounds (Cho), and 6.2 ؎ 0.9 mM for myo-inositol (Ins). The observation of relatively low tNAA and high Cho and Ins levels compared with cortical gray and white matter corresponds to a lower neuronal density and higher glial density than in the neocortex, in agreement with histologic findings. The data do not support a lateralization of metabolites. T1 and T2 relaxation times were in the range of 1400-1730 and 140-330 msec, respectively, similar to those in other brain regions. Magn

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“…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). In the first detailed analyses of Cr transporter expression in CNS, it was demonstrated that SLC6A8 is found in neurons and oligodendrocytes but, in contrast to AGAT and GAMT, cannot be detected in astrocytes ( Fig.…”

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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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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In situ hybridization analysis of CHOT1, a creatine transporter, in the rat central nervous system

Cited by 47 publications

References 35 publications

Brain Creatine Kinase and Creatine Transporter Proteins in Normal and Creatine-Treated Rabbit Pups

Brain Creatine Kinase and Creatine Transporter Proteins in Normal and Creatine-Treated Rabbit Pups

Localized proton MRS of the human hippocampus: Metabolite concentrations and relaxation times

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

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