Document Detail

The origin of deoxynucleosides in brain: implications for the study of neurogenesis and stem cell therapy.
MedLine Citation:
PMID:  17372683     Owner:  NLM     Status:  MEDLINE    
Detection of DNA synthesis in brain employing ((3)H)thymidine (((3)H)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 ((3)H)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 ((3)H)dT and/or BrdU methodologies can be useful if their limitations are recognized and they are used in conjunction with independent methods.
Reynold Spector; Conrad E Johanson
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Publication Detail:
Type:  Journal Article; Review     Date:  2007-03-20
Journal Detail:
Title:  Pharmaceutical research     Volume:  24     ISSN:  0724-8741     ISO Abbreviation:  Pharm. Res.     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-04-26     Completed Date:  2007-10-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  859-67     Citation Subset:  IM    
Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
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MeSH Terms
Brain / cytology,  embryology,  metabolism
Deoxyribonucleosides / biosynthesis*
Gene Therapy / methods
Models, Biological
Neurons / cytology,  metabolism*
Stem Cell Transplantation
Stem Cells / cytology,  metabolism
Reg. No./Substance:

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