ArticleAlcoholism, clinical and experimental research2014
Alcoholics have more tryptophan hydroxylase 2 mRNA and protein in the dorsal and median raphe nuclei.
Article in Alcoholism, clinical and experimental research, 2014. 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.
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- Association of Functional Polymorphism inGenes · 2023Article
- Neural serotonergic circuits for controlling long-term voluntary alcohol consumption in mice.Molecular psychiatry · 2022Article
- The regulatory role of AP-2β in monoaminergic neurotransmitter systems: insights on its signalling pathway, linked disorders and theragnostic potential.Cell & bioscience · 2022Review
- The role of microglia in neuropsychiatric disorders and suicide.European archives of psychiatry and clinical neuroscience · 2022Review
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- Hippocampal ceRNA networks from chronic intermittent ethanol vapor-exposed male mice and functional analysis of top-ranked lncRNA genes for ethanol drinking phenotypes.Advances in drug and alcohol research · 2022Article
- Translational Molecular Approaches in Substance Abuse Research.Handbook of experimental pharmacology · 2020Review
- Molecular windows into the human brain for psychiatric disorders.Molecular psychiatry · 2019Review
- Negative consequences of early-life adversity on substance use as mediated by corticotropin-releasing factor modulation of serotonin activity.Neurobiology of stress · 2018Review
- Adolescent intermittent ethanol reduces serotonin expression in the adult raphe nucleus and upregulates innate immune expression that is prevented by exercise.Brain, behavior, and immunity · 2017Article
- Alcohol and violence: neuropeptidergic modulation of monoamine systems.Annals of the New York Academy of Sciences · 2015Review
- Advances in Medications and Tailoring Treatment for Alcohol Use Disorder.Alcohol research : current reviews · 2015Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundChronic alcohol use depletes brain serotonin (5-hydroxytryptamine [5-HT]), yet we previously found more tryptophan hydroxylase 2 (TPH2), the rate-limiting biosynthetic enzyme for 5-HT, in the dorsal raphe nucleus (DRN) of alcoholics. We sought to determine whether the increase in amount of TPH2 enzyme is associated with more TPH2 mRNA gene expression in the DRN of a new cohort of alcoholics and controls.
methodsTPH2 mRNA and protein were measured by in situ hybridization and immunoautoradiography, respectively, in the DRN and median raphe nucleus (MRN) of age- and sex-matched pairs (n = 16) of alcoholics and nonpsychiatric controls. Alcohol use disorder diagnosis and medical, psychiatric, and family histories were obtained by psychological autopsy. Age and sex were covariates in the analyses.
resultsTPH2 mRNA in alcoholics was greater in the DRN and MRN compared to controls (DRN: controls: 3.6 ± 1.6, alcoholics: 4.8 ± 1.8 nCi/mg of tissue, F = 4.106, p = 0.02; MRN: controls: 2.6 ± 1.2, alcoholics: 3.5 ± 1.1 nCi/mg of tissue, F = 3.96, p = 0.024). The difference in TPH2 mRNA was present in all DRN subnuclei (dorsal [DRd]: 135%, interfascicular [DRif]: 139%, ventral [DRv]: 135%, ventrolateral [DRvl]: 136% of control p < 0.05) except the caudal subnucleus. Alcoholics also had more TPH2 protein in the DRN and MRN than controls (DRN: controls: 265 ± 47, alcoholics: 318 ± 47 μCi/g, F = 8.72, p = 0.001; MRN: controls: 250 ± 33, alcoholics: 345 ± 39 μCi/g, F = 7.78, p = 0.001). There is a positive correlation between TPH2 protein and mRNA expression in the DRN (r = 0.815, p < 0.001), suggesting that the higher amount of TPH2 protein is due to an increase in TPH2 gene expression.
conclusionsThese findings suggest that greater TPH2 gene expression is the basis for more TPH2 protein in the DRN and MRN in alcoholics.
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