ArticleThe Journal of biological chemistry2011
Partial biopterin deficiency disturbs postnatal development of the dopaminergic system in the brain.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- The vicious cycle of neuroinflammation and ferroptosis in depression: mechanisms and therapeutic targets.Frontiers in neuroscience · 2026Review
- Gene therapy for neurotransmitter-related disorders.Journal of inherited metabolic disease · 2024Review
- Baicalein Attenuates Brain Iron Accumulation through Protecting Aconitase 1 from Oxidative Stress in Rotenone-Induced Parkinson's Disease in Rats.Antioxidants (Basel, Switzerland) · 2022Article
- Tetrahydrobiopterin and Its Multiple Roles in Neuropsychological Disorders.Neurochemical research · 2022Review
- Insights into the expanding phenotypic spectrum of inherited disorders of biogenic amines.Nature communications · 2021Article
- Tetrahydrobioterin (BH4) Pathway: From Metabolism to Neuropsychiatry.Current neuropharmacology · 2021Review
- Sepiapterin reductase: Characteristics and role in diseases.Journal of cellular and molecular medicine · 2020Review
- Sepiapterin reductase gene-disrupted mice suffer from hypertension with fluctuation and bradycardia.Physiological reports · 2017Article
- Sulfa drugs inhibit sepiapterin reduction and chemical redox cycling by sepiapterin reductase.The Journal of pharmacology and experimental therapeutics · 2015Article
- Inactivation of ceramide synthase 6 in mice results in an altered sphingolipid metabolism and behavioral abnormalities.The Journal of biological chemistry · 2013Article
- Sepiapterin reductase mediates chemical redox cycling in lung epithelial cells.The Journal of biological chemistry · 2013Article
- Article
- Amelioration of behavioral abnormalities in BH(4)-deficient mice by dietary supplementation of tyrosine.PloS one · 2013Article
- Chronic 5-HT transporter blockade reduces DA signaling to elicit basal ganglia dysfunction.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Postnatal development of dopaminergic system is closely related to the development of psychomotor function. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the biosynthesis of dopamine and requires tetrahydrobiopterin (BH4) as a cofactor. To clarify the effect of partial BH4 deficiency on postnatal development of the dopaminergic system, we examined two lines of mutant mice lacking a BH4-biosynthesizing enzyme, including sepiapterin reductase knock-out (Spr(-/-)) mice and genetically rescued 6-pyruvoyltetrahydropterin synthase knock-out (DPS-Pts(-/-)) mice. We found that biopterin contents in the brains of these knock-out mice were moderately decreased from postnatal day 0 (P0) and remained constant up to P21. In contrast, the effects of BH4 deficiency on dopamine and TH protein levels were more manifested during the postnatal development. Both of dopamine and TH protein levels were greatly increased from P0 to P21 in wild-type mice but not in those mutant mice. Serotonin levels in those mutant mice were also severely suppressed after P7. Moreover, striatal TH immunoreactivity in Spr(-/-) mice showed a drop in the late developmental stage, when those mice exhibited hind-limb clasping behavior, a type of motor dysfunction. Our results demonstrate a critical role of biopterin in the augmentation of TH protein in the postnatal period. The developmental manifestation of psychomotor symptoms in BH4 deficiency might be attributable at least partially to high dependence of dopaminergic development on BH4 availability.
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