Back to Search
Start Over
Creatine salts provide neuroprotection even after partial impairment of the creatine transporter
- Source :
- Neuroscience
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Highlights • Creatine is a compound that is critical for energy metabolism of nervous cells. • Creatine absence due to deficit of creatine transporter causes severe brain symptoms. • Creatine crosses BBB and neuronal membrane slowly, and only using its transporter. • Creatine derivatives may cross BBB and neuronal membrane without the transporter. • Creatine derivatives may be a useful strategy in creatine transporter deficiency.<br />Creatine, a compound that is critical for energy metabolism of nervous cells, crosses the blood-brain barrier (BBB) and the neuronal plasma membrane with difficulty, and only using its specific transporter. In the hereditary condition where the creatine transporter is defective (creatine transporter deficiency) there is no creatine in the brain, and administration of creatine is useless lacking the transporter. The disease is severe and incurable. Creatine-derived molecules that could cross BBB and plasma membrane independently of the transporter might be useful to cure this condition. Moreover, such molecules could be useful also in stroke and other brain ischemic conditions. In this paper, we investigated three creatine salts, creatine ascorbate, creatine gluconate and creatine glucose. Of these, creatine glucose was ineffective after transporter block with guanidine acetic acid (GPA) administration. Creatine ascorbate was not superior to creatine in increasing tissue creatine and phosphocreatine content after transporter impairment, however even after such impairment it delayed synaptic failure during anoxia. Finally, creatine gluconate was superior to creatine in increasing tissue content of creatine after transporter block and slowed down PS disappearance during anoxia, an effect that creatine did not have. These findings suggest that coupling creatine to molecules having a specific transporter may be a useful strategy in creatine transporter deficiency. In particular, creatine ascorbate has effects comparable to those of creatine in normal conditions, while being superior to it under conditions of missing or impaired creatine transporter.
- Subjects :
- 0301 basic medicine
Male
Drug Evaluation, Preclinical
Ascorbic Acid
Hippocampus
Tissue Culture Techniques
chemistry.chemical_compound
0302 clinical medicine
creatine gluconate
creatine ascorbate
Medicine
CrT, creatine transporter
Guanidine
Hypoxia, Brain
Evoked Potentials
Mice, Inbred ICR
biology
Molecular Structure
Membrane transport protein
General Neuroscience
Neuroprotective Agents
GPA, guanidine acetic acid
neuroprotection
medicine.medical_specialty
BBB, blood-brain barrier
creatine transporter deficiency
Neuroscience(all)
Creatine
Neuroprotection
Gluconates
Article
Phosphocreatine
03 medical and health sciences
Internal medicine
creatine
creatine glucose
Animals
TLC, thin layer chromatography
business.industry
Membrane Transport Proteins
Transporter
Ascorbic acid
030104 developmental biology
Endocrinology
Glucose
chemistry
nervous system
biology.protein
Creatine kinase
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 03064522
- Volume :
- 340
- Database :
- OpenAIRE
- Journal :
- Neuroscience
- Accession number :
- edsair.doi.dedup.....36a2d15f531b491b64d4089bcfcc5a9b
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2016.02.038