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Alcoholics Have More Tryptophan Hydroxylase 2 mRNA and Protein in the Dorsal and Median Raphe Nuclei
Author(s) -
Bach Helene,
Arango Victoria,
Kassir Suham A.,
Tsaava Tea,
Dwork Andrew J.,
Mann J. John,
Underwood Mark D.
Publication year - 2014
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12414
Subject(s) - dorsal raphe nucleus , raphe nuclei , tryptophan hydroxylase , messenger rna , serotonergic cell groups , dorsum , chemistry , medicine , biology , serotonin , anatomy , biochemistry , serotonergic , gene , receptor
Background Chronic alcohol use depletes brain serotonin (5‐hydroxytryptamine [5‐ HT ]), yet we previously found more tryptophan hydroxylase 2 ( TPH 2), 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. Methods TPH2 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. Results TPH2 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 μ Ci/g, F = 8.72, p = 0.001; MRN: controls: 250 ± 33, alcoholics: 345 ± 39 μ Ci/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. Conclusions These findings suggest that greater TPH 2 gene expression is the basis for more TPH 2 protein in the DRN and MRN in alcoholics.