Regional Distribution and Cellular Expression of Tryptophan Hydroxylase Messenger RNA in Postmortem Human Brainstem and Pineal Gland

Abstract

Abstract:The characterization and cellular localization of tryptophan hydroxylase mRNA in the human brainstem and pineal gland were investigated by using northern blot analysis and in situ hybridization histochemistry. Northern analysis of human pineal gland revealed the presence of two mRNA species that were absent in RNA isolated from human raphe. In situ hybridization experiments revealed very dense hybridization signal corresponding to tryptophan hydroxylase mRNA in cells throughout the pineal gland. In contrast, tryptophan hydroxylase mRNA was heterogeneously distributed in neurons in the dorsal and median raphe nuclei. Within the dorsal raphe, the ventrolateral and interfascicular subnuclei contained the greatest number of tryptophan hydroxylase mRNA-positive neurons. Also, the cellular concentration of tryptophan hydroxylase mRNA varied widely within the dorsal and median raphe. Comparison of the cellular concentration of tryptophan hydroxylase mRNA between the pineal gland and the raphe nuclei revealed an 11 -and 46-fold greater average grain density of tryptophan hydroxylase mRNA positive cells in the pineal gland compared with the dorsal and median raphe, respectively. These findings are the first to demonstrate the cellular localization of tryptophan hydroxylase mRNA in the human brain and pineal gland as well as heterogeneity in the cellular concentration within and between these tissues.

Stress Upregulates TPH1 but not TPH2 mRNA in the Rat Dorsal Raphe Nucleus: Identification of Two TPH2 mRNA Splice Variants

“…If this probe was hybridizing to TPH2 sequences it would have also been detectable in the DRN of control rats. Thus, the present data provide evidence for the existence of TPH1 mRNA in the DRN, in accordance with previous reports (Dumas et al 1989;Huh et al 1994;Austin and O'Donnell 1999;Gundlah et al 2005).…”

Altered expression of neuronal tryptophan hydroxylase-2 mRNA in the dorsal and median raphe nuclei of three genetically modified mouse models relevant to depression and anxiety

“…DRN, known to contain fewer serotonergic neurons (Steinbusch, 1981), suggests that the DRL may be less involved in this model. In agreement with our data, previous studies already reported a heterogeneous distribution of TPH2 mRNA in the DRN with the greatest number of TPH2 mRNA-positive neurons in the DRD and DRV subnuclei (Austin and O'Donnell, 1999;Clark et al, 2006). Perhaps, the DRL exhibits a lower sensitivity to extracellular 5-HT levels and consequently does not display any alteration in TPH2 expression.…”

Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism

“…3 ) Genes that are transcriptionally repressed by vitamin D hormone have a high basal mRNA expression in the absence of vitamin D; however, on vitamin D hormone binding, mRNA expression is downregulated (90). This is in agreement with the high mRNA expression levels of TPH1 in human pineal gland, which is 150 times higher than TPH2 in the brainstem (97). 4 ) Serotonin in the blood, which is produced from TPH1, is lowest in summer months and highest in winter, whereas brain serotonin, which is generated from TPH2, is highest in summer months and lowest in winter months (98–100).…”