title: Spatio-temporal expression of tryptophan hydroxylase isoforms in murine and human brain: convergent data from Tph2 knockout mice.
abstract: Dysregulation of tryptophan hydroxylase (TPH)-dependent serotonin (5-HT) synthesis, has been implicated in various neuropsychiatric disorders, although the differential expression pattern of the two isoforms is controversial. Here, we report a comprehensive spatio-temporal isoform-specific analysis of TPH1 and TPH2 expression during pre- and postnatal development of mouse brain and in adult human brain. TPH2 expression was consistently detected in the raphe nuclei, as well as in fibers in the deep pineal gland and in small intestine. Although TPH1 expression was found in these peripheral tissues, no significant TPH1 expression was detected in the brain, neither during murine development, nor in mouse and human adult brain. In support of TPH2 specificity in brain 5-HT synthesis, raphe neurons of Tph2 knockout mice were completely devoid of 5-HT, with no compensatory activation of Tph1 expression. In conclusion, our findings indicate that brain 5-HT synthesis across the lifespan is exclusively maintained by TPH2.
authors.affiliation: Molecular and Clinical Psychobiology, Department of Psychiatry, Psychosomatics, and Psychotherapy, University of Wuerzburg, Fuechsleinstrasse 15, 97080 Wuerzburg, Germany. Gutknecht_L@klinik.uni-wuerzburg.de
authors.forename: Lise
authors.initials: L
authors.lastname: Gutknecht
authors.forename: Claudia
authors.initials: C
authors.lastname: Kriegebaum
authors.forename: Jonas
authors.initials: J
authors.lastname: Waider
authors.forename: Angelika
authors.initials: A
authors.lastname: Schmitt
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D020033:Protein Isoforms; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase