The maturation of the serotonergic system and its effects on the development of the dopaminergic system during chicken mid-late embryogenesis

Authors: HUANG, X - Purdue University; KUANG, S - Purdue University; APPLEGATE, T - University Of Georgia; LIN, T - Purdue University; Cheng, Heng-Wei

Submitted to: Molecular and Cellular Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/31/2019
Publication Date: 6/2/2019
Citation: Huang, X.H., Kuang, S.H., Applegate, T., Lin, T.L., Cheng, H. 2019. The maturation of the serotonergic system and its effects on the development of the dopaminergic system during chicken mid-late embryogenesis. Molecular and Cellular Endocrinology. https://doi.org/10.1016/j.mce.2019.110472.
DOI: https://doi.org/10.1016/j.mce.2019.110472

Interpretive Summary: Serotonin acts as a neurotransmitter regulating multiple biological functions with lifelong effects on animal physical, physiological and mental health. Its dysfunction during embryonic development causes long-lasting brain structural and functional alterations in humans and rodents, such as serotonin deficiency-associated aggression. The current results showed that there is a critical phase for the development of the serotonergic system during the mid-late embryogenesis; and during this embryonic period, serotonin directly and indirectly regulates the development and functions of the brain. The results can be used by scientists for further investigating if aggression could be reduced or inhibited by prenatally modulating the serotonergic system in poultry as well as in other farm animals.

Technical Abstract: Serotonin (5-HT) acts as a morphogen influencing embryonic brain development, and as a neurotransmitter regulating multiple biological functions with lifelong effects on animal physical, physiological and mental health, especially during the rapid growth phase prior to birth when embryos face many challenges to reach structural and functional completion. In this study, the development of the serotonergic (5-HTergic) system and its modulatory effect on the dopaminergic (DAergic) system and related neural circuits were investigated during mid-late embryogenesis, embryonic day (E)12-E20, in the chicken’s brain. During 5-HTergic neuronal maturation, a growth-related anatomical and functional remodeling was highlighted: the 5-HT neurons continuously grew during E12-E20 except for a remarkable regression during E14-E16. Correspondingly, there was a time-dependent change in the 5-HT synthetic capacity. Specifically, 5-HT concentrations in the raphe nuclei increased from E12 to E14, reaching a plateau during E14-E16, then continuously increased up to E19, and reaching a second plateau between E19-E20. The second plateau of the 5-HT concentration was in correspondence with the establishment of the 5-HTergic autoregulatory loop during E19-E20 and the development of the DAergic system. The DA concentrations remained unchanged from E12 to E16, then started to increase at E16, reaching a maximum at E19, and diminished before hatching. The unique developmental time sequence between the 5-HTergic and DAergic systems suggests that the maturation of the 5-HTergic system may regulate the development of the DAergic neurons during the mid-late chicken embryogenesis, while DA may regulate the hatching events. These results provide new insights for understanding the functional organization of the 5-HTergic system during embryonic development and raise the possibility that prenatally modulating the 5-HTergic system may lead to long-lasting brain structural and functional alterations.