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The Origin of Deoxynucleosides in Brain: Implications for the Study of Neurogenesis and Stem Cell Therapy

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Abstract

Detection of DNA synthesis in brain employing (3H)thymidine ((3H)dT) or bromo deoxyuridine (BrdU) is widely used as a measure of the “birth” of cells in brain development, adult neurogenesis and neuronal stem cell replacement strategies. However, recent studies have raised serious questions about whether this methodology adequately measures the “birth” of cells in brain either quantitatively or in an interpretable way in comparative studies, or in stem cell investigations. To place these questions in perspective, we review deoxynucleoside synthesis and pharmacokinetics focusing on the barriers interfacing the blood-brain (cerebral capillaries) and blood-cerebrospinal fluid (choroid plexus), and the mechanisms, molecular biology and location of the deoxynucleoside transport systems in the central nervous system. Brain interstitial fluid and CSF nucleoside homeostasis depend upon the activity of concentrative nucleoside transporters (CNT) on the ‘central side’ of the barrier cells and equilibrative nucleoside transporters (ENT) on their ‘plasma side.’ With this information about nucleoside transporters, blood/CSF concentrations and metabolic pathways, we discuss the assumptions and weaknesses of using (3H)dT or BrdU methodologies alone for studying DNA synthesis in brain in the context of neurogenesis and potential stem cell therapy. We conclude that the use of (3H)dT and/or BrdU methodologies can be useful if their limitations are recognized and they are used in conjunction with independent methods.

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Acknowledgements

The authors thank Michiko Spector for her aid in the preparation of the manuscript and Julie Johanson for assistance with graphics.

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Authors and Affiliations

  1. Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

    Reynold Spector

  2. Harvard-MIT Program in the Health Sciences, Cambridge, Massachusetts, USA

    Reynold Spector

  3. Brown Medical School, Providence, Rhode Island, USA

    Conrad E. Johanson

  4. Dept. of Neurosurgery, Rhode Island Hospital, 593 Eddy Street, Providence, Rhode Island, 02903, USA

    Conrad E. Johanson

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  1. Reynold Spector
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  2. Conrad E. Johanson
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Correspondence to Conrad E. Johanson.

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Spector, R., Johanson, C.E. The Origin of Deoxynucleosides in Brain: Implications for the Study of Neurogenesis and Stem Cell Therapy. Pharm Res 24, 859–867 (2007). https://doi.org/10.1007/s11095-006-9221-0

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  • DOI: https://doi.org/10.1007/s11095-006-9221-0

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