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Protective Effects of Some Creatine Derivatives in Brain Tissue Anoxia

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Abstract

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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Abbreviations

ACSF:

Artificial cerebrospinal fluid

ADP:

Adenosine diphospate

ATP:

Adenosine triphosphate

CA1:

Cornu Ammonis, field 1

DC:

Direct current

GPA:

3-Guanidinopropionic acid

HPLC:

High-performance liquid chromatography

RP-HPLC:

Reverse-phase high-performance liquid chromatography

TLC:

Thin layer chromatography

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Acknowledgements

This work was supported by INTAS (International Association for the promotion of co-operation with scientists from the New Independent States of the former Soviet Union, grant 441/00) and by Telethon Italy (grant GGP04092).

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Authors and Affiliations

  1. Department of Neuroscience, Ophthalmology and Genetics, University of Genova, Via De Toni 5, Genova, 16132, Italy

    Luisa Perasso, Federica Risso, Carlo Gandolfo & Maurizio Balestrino

  2. Section of Pharmacology, Department of Oncology, Biology and Genetics, University of Genova, Genova, Italy

    Gian Luigi Lunardi & Tullio Florio

  3. Institute of Macromolecular Compounds, Russian Academy of Sciences, St. Petersburg, Russia

    Anna V. Pohvozcheva, Maria V. Leko & Sergey V. Burov

  4. Institute of Bioimaging and Molecular Physiology, Section of Genova, National Research Council (CNR), Genova, Italy

    Aroldo Cupello

Authors
  1. Luisa Perasso
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  2. Gian Luigi Lunardi
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  4. Anna V. Pohvozcheva
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  10. Maurizio Balestrino
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Correspondence to Maurizio Balestrino.

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Perasso, L., Lunardi, G.L., Risso, F. et al. Protective Effects of Some Creatine Derivatives in Brain Tissue Anoxia. Neurochem Res 33, 765–775 (2008). https://doi.org/10.1007/s11064-007-9492-9

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  • DOI: https://doi.org/10.1007/s11064-007-9492-9

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