ArticleACS chemical neuroscience2016
Regulation of Tyrosine Hydroxylase Expression and Phosphorylation in Dopamine Transporter-Deficient Mice.
Article in ACS chemical neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 73 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Deletion of N-ethylmaleimide-sensitive factor in dopamine D2 receptor-expressing cells impairs striatal development and dopaminergic function and induces ADHD-like behaviors in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Effects of Maternal Tetramethyl Bisphenol F Exposure on Neurodevelopment and Behavior in Mouse Offspring.International journal of molecular sciences · 2026Article
- Tyrosine Hydroxylase Deficiency Impairs TH Axonal Transport, Brain Function, and Neuronal Plasticity.Journal of inherited metabolic disease · 2026Article
- Dorsal Raphe VIP Neurons Are Critical for Survival-Oriented Vigilance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Osmotin-derived 9-amino-acid peptide alleviates α-synuclein and MPTP-induced glial cell activation mediated neuroinflammation, protecting dopaminergic neurons in Parkinson's disease mice brain.Journal of biomedical science · 2026Article
- Computational modelling identifies key determinants of subregion-specific dopamine dynamics in the striatum.eLife · 2026Article
- The neuromodulatory effects ofFood science and biotechnology · 2025Article
- Stable Dopamine-Signaling mRNA Co-Expression in the Substantia Nigra Is Deregulated in Pathological Conditions, but Not in Dopamine Transporter Knockout Rats.Biomolecules · 2025Article
- Central biogenic amine deficiency with concomitant exploratory behavioral deficits in Dnajc12 knock-out mice.NPJ Parkinson's disease · 2025Article
- The Ins and Outs of Dopamine Transporter Gene Manipulation: In Vivo Models of DAT Dysfunction.Advances in neurobiology · 2025Review
- Phosphodiesterase inhibition and Gucy2C activation enhance tyrosine hydroxylase Ser40 phosphorylation and improve 6-hydroxydopamine-induced motor deficits.Cell & bioscience · 2024Article
- Tyrosine Hydroxylase Inhibitors and Dopamine Receptor Agonists Combination Therapy for Parkinson's Disease.International journal of molecular sciences · 2024Review
- Dopamine Signaling in Substantia Nigra and Its Impact on Locomotor Function-Not a New Concept, but Neglected Reality.International journal of molecular sciences · 2024Review
- Effects of Multiple High-Dose Methamphetamine Administration on Enteric Dopaminergic Neurons and Intestinal Motility in the Rat Model.Neurotoxicity research · 2023Article
- The gut microbiota metabolite butyrate mitigates MPTP/MPPThe Kaohsiung journal of medical sciences · 2023Article
- Striatal serotonin transporter gain-of-function in L-DOPA-treated, hemi-parkinsonian rats.Brain research · 2023Article
- Dopamine Transporter Deficient Rodents: Perspectives and Limitations for Neuroscience.Biomolecules · 2023Review
- Targeting dopamine transporter to ameliorate cognitive deficits in Alzheimer's disease.Frontiers in cellular neuroscience · 2023Review
- Heterozygote Dopamine Transporter Knockout Rats Display Enhanced Cocaine Locomotion in Adolescent Females.International journal of molecular sciences · 2022Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Tyrosine hydroxylase (TH) and dopamine transporters (DATs) regulate dopamine (DA) neurotransmission at the biosynthesis and reuptake steps, respectively. Dysfunction or loss of these proteins occurs in impaired locomotor or addictive behavior, but little is known about the influence of DAT expression on TH function. Differences in TH phosphorylation, DA tissue content, l-DOPA biosynthesis, and DA turnover exist between the somatodendritic and terminal field compartments of nigrostriatal and mesoaccumbens pathways. We examined whether differential DAT expression affects these compartmental differences in DA regulation by comparing TH expression and phosphorylation at ser31 and ser40. In heterozygous DAT knockout (KO) (+/-) mice, DA tissue content and DA turnover were unchanged relative to wild-type mice, despite a 40% reduction in DAT protein expression. In DAT KO (-/-) mice, DA turnover increased in all DA compartments, but DA tissue content decreased (90-96%) only in terminal fields. TH protein expression and phosphorylation were differentially affected within DA pathway compartments by relative expression of DAT. TH protein decreased (∼74%), though to a significantly lesser extent than DA, in striatum and nucleus accumbens (NAc) in DAT -/- mice, with no decrease in substantia nigra or ventral tegmental area. Striatal ser31 TH phosphorylation and recovery of DA relative to TH protein expression in DAT +/- and DAT -/- mice decreased, whereas ser40 TH phosphorylation increased ∼2- to 3-fold in striatum and NAc of DAT -/- mice. These results suggest that DAT expression affects TH expression and phosphorylation largely in DA terminal field compartments, further corroborating evidence for dichotomous regulation of TH between somatodendritic and terminal field compartments of the nigrostriatal and mesoaccumbens pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.