Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Peripherally administered reduced pterins do enter the brain

G Kapatos, S Kaufman

    Science (New York, N.Y.)
    |May 22, 1981
    PubMed
    Summary

    Administered tetrahydrobiopterin increased rat brain levels. A model pteridine, 6-methyltetrahydropterin, more effectively crossed the blood-brain barrier, suggesting potential for treating neurological disorders.

    Related Concept Videos

    You might also read

    Related Articles

    Articles linked to this work by shared authors, journal, and citation graph.

    Sort by
    Same author

    Study of a Swiss dopa-responsive dystonia family with a deletion in GCH1: redefining DYT14 as DYT5.

    Neurology·2007
    Same author

    Characterization of GTP cyclohydrolase I gene expression in the human neuroblastoma SKN-BE(2)M17: enhanced transcription in response to cAMP is conferred by the proximal promoter.

    Journal of neurochemistry·2001
    Same author

    Effects of NADH on dopamine release in rat striatum.

    Synapse (New York, N.Y.)·2000
    Same author

    Identification and characterization of basal and cyclic AMP response elements in the promoter of the rat GTP cyclohydrolase I gene.

    The Journal of biological chemistry·2000
    Same author

    Prenatal ethanol reduces the activity of adult midbrain dopamine neurons.

    Alcoholism, clinical and experimental research·1999
    Same author

    Cloning and expression of recombinant human pineal tryptophan hydroxylase in Escherichia coli: purification and characterization of the cloned enzyme.

    Biochimica et biophysica acta·1999

    Area of Science:

    • Neuroscience
    • Biochemistry
    • Pharmacology

    Background:

    • Tetrahydrobiopterin (BH4) is a crucial cofactor for neurotransmitter synthesis.
    • Defects in BH4 metabolism cause neurological disorders like hyperphenylalaninemia.
    • Understanding BH4 transport across the blood-brain barrier (BBB) is vital for therapeutic strategies.

    Purpose of the Study:

    • To investigate the efficacy of peripheral tetrahydrobiopterin administration on rat brain BH4 levels.
    • To evaluate the blood-brain barrier penetration and brain retention of a model pteridine, 6-methyltetrahydropterin.
    • To explore the potential of reduced pterin replacement therapy for CNS disorders linked to BH4 deficiency.

    Main Methods:

    • Peripheral administration of tetrahydrobiopterin and 6-methyltetrahydropterin to rats.
    • Measurement of tetrahydrobiopterin and 6-methyltetrahydropterin concentrations in rat brain tissue.
    • Pharmacokinetic analysis of 6-methyltetrahydropterin in striatum, including half-life determination.

    Main Results:

    • Peripherally administered tetrahydrobiopterin doubled rat brain tetrahydrobiopterin content, with the natural diastereoisomer being more effective.
    • 6-methyltetrahydropterin demonstrated 10-fold greater efficiency in crossing the blood-brain barrier compared to tetrahydrobiopterin.
    • Striatal 6-methyltetrahydropterin levels remained elevated for 2 hours with a 3-hour half-life; it was localized to nerve terminals.

    Conclusions:

    • Peripheral tetrahydrobiopterin administration can increase brain tetrahydrobiopterin levels.
    • 6-methyltetrahydropterin exhibits favorable blood-brain barrier penetration and brain retention characteristics.
    • Reduced pterin therapy, potentially using analogs like 6-methyltetrahydropterin, shows promise for treating central nervous system disorders associated with tetrahydrobiopterin deficiencies.

    Related Experiment Videos