Journal
EUROPEAN NEUROPSYCHOPHARMACOLOGY
Volume 19, Issue 4, Pages 266-282Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.euroneuro.2008.12.005
Keywords
Tph1; Tph2; Serotonin; Development; Raphe nuclei; Pineal gland
Funding
- Deutsche Forschungsgemeinschaft
- European Commission [NEWMOOD LSHMCT-2003-503474]
- Bundesministerium fur Bildung und Forschung [IZKF 01 KS 9603]
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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. (c) 2008 Elsevier B.V. and ECNP. All rights reserved.
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