ArticleFrontiers in psychiatry2012
Dopamine pathology in schizophrenia: analysis of total and phosphorylated tyrosine hydroxylase in the substantia nigra.
Article in Frontiers in psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- Increased Tumor Necrosis Factor Superfamily Members in Neuroinflammatory Schizophrenia and Bipolar Disorder Midbrains.Biological psychiatry global open science · 2026Article
- Schizophrenia-associated changes in neuronal subpopulations in the human midbrain.Brain : a journal of neurology · 2025Article
- Cell line specific alterations in genes associated with dopamine metabolism and signaling in midbrain dopaminergic neurons derived from 22q11.2 deletion carriers with elevated dopamine synthesis capacity.Schizophrenia research · 2024Article
- CPT2 Deficiency Modeled in Zebrafish: Abnormal Neural Development, Electrical Activity, Behavior, and Schizophrenia-Related Gene Expression.Biomolecules · 2024Article
- Standardized Data Acquisition for Neuromelanin-sensitive Magnetic Resonance Imaging of the Substantia Nigra.Journal of visualized experiments : JoVE · 2021Article
- Actualities in immunological markers and electrochemical sensors for determination of dopamine and its metabolites in psychotic disorders (Review).Experimental and therapeutic medicine · 2021Review
- Markers of copper transport in the cingulum bundle in schizophrenia.Schizophrenia research · 2021Article
- Evidence for altered excitatory and inhibitory tone in the post-mortem substantia nigra in schizophrenia.The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry · 2020Article
- Impaired brain glucose metabolism and presynaptic dopaminergic functioning in a mouse model of schizophrenia.EJNMMI research · 2020Article
- Intracellular compartment-specific proteasome dysfunction in postmortem cortex in schizophrenia subjects.Molecular psychiatry · 2020Article
- Increased Macrophages and C1qA, C3, C4 Transcripts in the Midbrain of People With Schizophrenia.Frontiers in immunology · 2020Article
- G Protein-Coupled Receptors (GPCRs)-Mediated Calcium Signaling in Ovarian Cancer: Focus on GPCRs activated by Neurotransmitters and Inflammation-Associated Molecules.International journal of molecular sciences · 2019Review
- Pathology of white matter integrity in three major white matter fasciculi: A post-mortem study of schizophrenia and treatment status.British journal of pharmacology · 2019Article
- Neuromelanin-sensitive MRI as a noninvasive proxy measure of dopamine function in the human brain.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Substantia nigra ultrastructural pathology in schizophrenia.Schizophrenia research · 2018Article
- Nigral Stress-Induced Dopamine Release in Clinical High Risk and Antipsychotic-Naïve Schizophrenia.Schizophrenia bulletin · 2018Article
- Psychosis in Spinocerebellar Ataxias: a Case Series and Study of Tyrosine Hydroxylase in Substantia Nigra.Cerebellum (London, England) · 2018Article
- Overexpression of Thioredoxin-1 Blocks Morphine-Induced Conditioned Place Preference Through Regulating the Interaction of γ-Aminobutyric Acid and Dopamine Systems.Frontiers in neurology · 2018Article
- Putative presynaptic dopamine dysregulation in schizophrenia is supported by molecular evidence from post-mortem human midbrain.Translational psychiatry · 2017Article
- Protein Markers of Neurotransmitter Synthesis and Release in Postmortem Schizophrenia Substantia Nigra.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
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5 authors at 1 institution in 1 country.
Funding
Abstract
introductionDespite the importance of dopamine neurotransmission in schizophrenia, very few studies have addressed anomalies in the mesencephalic dopaminergic neurons of the substantia nigra/ventral tegmental area (SN/VTA). Tyrosine hydroxylase (TH) is the rate-limiting enzyme for the production of dopamine, and a possible contributor to the anomalies in the dopaminergic neurotransmission observed in schizophrenia.
objectivesIn this study, we had three objectives: (1) Compare TH expression (mRNA and protein) in the SN/VTA of schizophrenia and control postmortem samples. (2) Assess the effect of antipsychotic medications on the expression of TH in the SN/VTA. (3) Examine possible regional differences in TH expression anomalies within the SN/VTA.
methodsTo achieve these objectives three independent studies were conducted: (1) A pilot study to compare TH mRNA and TH protein levels in the SN/VTA of postmortem samples from schizophrenia and controls. (2) A chronic treatment study was performed in rodents to assess the effect of antipsychotic medications in TH protein levels in the SN/VTA. (3) A second postmortem study was performed to assess TH and phosphorylated TH protein levels in two types of samples: schizophrenia and control samples containing the entire rostro-caudal extent of the SN/VTA, and schizophrenia and control samples containing only mid-caudal regions of the SN/VTA. RESULTS AND
conclusionOur studies showed impairment in the dopaminergic system in schizophrenia that could be mainly (or exclusively) located in the rostral region of the SN/VTA. Our studies also showed that TH protein levels were significantly abnormal in schizophrenia, while mRNA expression levels were not affected, indicating that TH pathology in this region may occur posttranscriptionally. Lastly, our antipsychotic animal treatment study showed that TH protein levels were not significantly affected by antipsychotic treatment, indicating that these anomalies are an intrinsic pathology rather than a treatment effect.
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