M Elizabeth Meredith1, James M May. 1. Department of Molecular Physiology and Biophysics, Vanderbilt University, 2213 Garland Avenue, 7465 MRBIV, Nashville, TN 37232-0465, USA. Electronic address: Elizabeth.meredith@Vanderbilt.edu.
Abstract
SCOPE: Ascorbic acid (ascorbate) is required to recycle tetrahydrobiopterin, which is necessary for neurotransmitter synthesis by the rate-limiting enzymes tyrosine and tryptophan hydroxylases. We sought to determine whether ascorbate might regulate embryonic brain cortex monoamine synthesis utilizing transgenic mouse models with varying intracellular ascorbate levels. METHODS AND RESULTS: In embryos lacking the sodium-dependent vitamin C transporter 2 (SVCT2), very low levels of brain ascorbate decreased cortex levels of norepinephrine and dopamine by approximately 33%, but had no effect on cortex serotonin or its metabolite, 5-hydroxyindole acetic acid. This decrease in ascorbate also led to a decrease in protein levels of tyrosine hydroxylase, but not of tryptophan hydroxylase. Increased cortex ascorbate in embryos carrying extra copies of the SVCT2 resulted in increased levels of dopamine and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), as well as serotonin and 5-hydroxyindole acetic acid. CONCLUSION: The dependence of embryonic brain cortex neurotransmitter synthesis and tyrosine hydroxylase expression on intracellular ascorbate emphasizes the importance of receiving adequate ascorbate during development.
SCOPE: Ascorbic acid (ascorbate) is required to recycle tetrahydrobiopterin, which is necessary for neurotransmitter synthesis by the rate-limiting enzymes tyrosine and tryptophan hydroxylases. We sought to determine whether ascorbate might regulate embryonic brain cortexmonoamine synthesis utilizing transgenic mouse models with varying intracellular ascorbate levels. METHODS AND RESULTS: In embryos lacking the sodium-dependent vitamin C transporter 2 (SVCT2), very low levels of brain ascorbate decreased cortex levels of norepinephrine and dopamine by approximately 33%, but had no effect on cortex serotonin or its metabolite, 5-hydroxyindole acetic acid. This decrease in ascorbate also led to a decrease in protein levels of tyrosine hydroxylase, but not of tryptophan hydroxylase. Increased cortex ascorbate in embryos carrying extra copies of the SVCT2 resulted in increased levels of dopamine and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), as well as serotonin and 5-hydroxyindole acetic acid. CONCLUSION: The dependence of embryonic brain cortex neurotransmitter synthesis and tyrosine hydroxylase expression on intracellular ascorbate emphasizes the importance of receiving adequate ascorbate during development.
Authors: Sotiria Sotiriou; Suzana Gispert; Jun Cheng; Yaohui Wang; Amy Chen; Shelley Hoogstraten-Miller; Georgina F Miller; Oran Kwon; Mark Levine; Susan H Guttentag; Robert L Nussbaum Journal: Nat Med Date: 2002-05 Impact factor: 53.440
Authors: Stefan R Bornstein; Mayumi Yoshida-Hiroi; Sotiria Sotiriou; Mark Levine; Hans-Georg Hartwig; Robert L Nussbaum; Graeme Eisenhofer Journal: FASEB J Date: 2003-08-01 Impact factor: 5.191