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Abstract

Existence of the gastro-intestinal peptide secretin in the CNS has been a matter of debate, and contrasting results have been reported, altogether indicating that the CNS is not a major site of production of this peptide. A thorough analysis was conducted in brain of transgenic mice in which the expression of the early region of simian virus 40 large T antigen (Tag) is under control of the rat secretin gene promoter. We studied Tag expression in the brains of E14–P90 transgenic mice as well as secretin mRNA and protein expression in transgenic and control CD1 mice at corresponding developmental stages. We show here a perfect correspondence of Tag and secretin mRNA expression in the mesencephalon of transgenic and normal mice between E14 and birth. In embryos, Tag is also expressed in the spinal cord, as well as in several areas of the peripheral nervous system. Localization of Tag in P0–P90 animals becomes restricted to a single compact cellular mass in mesencephalon at the level of the dorsal raphe, raphe magnus and lateral paragigantocellular nuclei. Neurons of these nuclei display secretin mRNA from E14 to birth, in both control CD1 and transgenic mice. Approximately half of these secretin-expressing neurons are immunoreactive for serotonin (5HT) and/or tryptophan hydroxylase. These results demonstrate that the secretin gene is transiently expressed in mouse serotoninergic mesencephalic neurons during development. In addition our data suggest a trophic role for secretin on neurons known to be involved in multiple superior functions in the normal brain, and lost in neurodegenerative disorders.