ArticleAnnals of neurology2014
Loss of dopamine phenotype among midbrain neurons in Lesch-Nyhan disease.
Article in Annals of neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- One-Carbon Metabolism and Midbrain Dopaminergic Cells in Lesch-Nyhan Disease.Molecular syndromology · 2026Review
- A new conditional mouse model for Cre-mediated restoration ofbioRxiv : the preprint server for biology · 2026Article
- Dental Management of Self-Injurious Behavior in Lesch-Nyhan Disease: A Patient- and Caregiver-Reported Outcome Study.Children (Basel, Switzerland) · 2026Article
- Changes in Purine Metabolism During Differentiation of Dopamine Neurons from Human Induced Pluripotent Stem Cells.Cellular and molecular neurobiology · 2026Article
- Uncovering Proteomic and Biochemical Alterations in Plasma from Lesch-Nyhan Disease Patients.Cellular and molecular neurobiology · 2025Article
- Purine Metabolism and Dystonia: Perspectives of a Long-Promised Relationship.Annals of neurology · 2025Review
- The Role of Purine Metabolism and Uric Acid in Postnatal Neurologic Development.Molecules (Basel, Switzerland) · 2025Review
- Unleashing the Power of Induced Pluripotent stem Cells in in vitro Modelling of Lesch-Nyhan Disease.Stem cell reviews and reports · 2025Review
- Epigenetic modulation of human neurobiological disorders: Lesch-Nyhan disease as a model disorder.AIMS neuroscience · 2025Review
- Inborn Errors of Purine Salvage and Catabolism.Metabolites · 2023Review
- Dysuricemia-A New Concept Encompassing Hyperuricemia and Hypouricemia.Biomedicines · 2023Review
- Rare variants in IMPDH2 cause autosomal dominant dystonia in Chinese population.Journal of neurology · 2023Article
- HGprt deficiency disrupts dopaminergic circuit development in a genetic mouse model of Lesch-Nyhan disease.Cellular and molecular life sciences : CMLS · 2022Article
- Encephalomalacia/gliosis, deep venous thrombosis, and cancer in Arg393His antithrombin Hanoi and the potential impact of the β-amyloid precursor protein (APP) on thrombosis and cancer.AIMS neuroscience · 2022Review
- Microstructural white matter abnormalities in Lesch-Nyhan disease.The European journal of neuroscience · 2022Article
- Case report: Early-onset renal failure as presenting sign of Lesch-Nyhan disease in infancy.Frontiers in pediatrics · 2022Article
- Deep brain stimulation in Lesch-Nyhan disease: outcomes from the patient's perspective.Developmental medicine and child neurology · 2021Article
- Lesch-Nyhan disease causes impaired energy metabolism and reduced developmental potential in midbrain dopaminergic cells.Stem cell reports · 2021Article
- DNA Repair in Huntington's Disease and Spinocerebellar Ataxias: Somatic Instability and Alternative Hypotheses.Journal of Huntington's disease · 2021Review
- Potential molecular link between the β-amyloid precursor protein (APP) and hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme in Lesch-Nyhan disease and cancer.AIMS neuroscience · 2021Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveLesch-Nyhan disease (LND) is caused by congenital deficiency of the purine recycling enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt). Affected patients have a peculiar neurobehavioral syndrome linked with reductions of dopamine in the basal ganglia. The purpose of the current studies was to determine the anatomical basis for the reduced dopamine in human brain specimens collected at autopsy.
methodsHistopathological studies were conducted using autopsy tissue from 5 LND cases and 6 controls. Specific findings were replicated in brain tissue from an HGprt-deficient knockout mouse using immunoblots, and in a cell model of HGprt deficiency by flow-activated cell sorting (FACS).
resultsExtensive histological studies of the LND brains revealed no signs suggestive of a degenerative process or other consistent abnormalities in any brain region. However, neurons of the substantia nigra from the LND cases showed reduced melanization and reduced immunoreactivity for tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis. In the HGprt-deficient mouse model, immunohistochemical stains for TH revealed no obvious loss of midbrain dopamine neurons, but quantitative immunoblots revealed reduced TH expression in the striatum. Finally, 10 independent HGprt-deficient mouse MN9D neuroblastoma lines showed no signs of impaired viability, but FACS revealed significantly reduced TH immunoreactivity compared to the control parent line.
interpretationThese results reveal an unusual phenomenon in which the neurochemical phenotype of dopaminergic neurons is not linked with a degenerative process. They suggest an important relationship between purine recycling pathways and the neurochemical integrity of the dopaminergic phenotype.
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