Topic: TPH2

Previous studies from our group showed that brain serotonin deficiency in rodents affects the early postnatal growth of the pups, triggering behavioral alterations and problems in social communication. We aim at understanding the causal link between low levels of brain serotonin and growth retardation and altered behavior in the early postnatal phase of development. To do this we are using a knockout rat model lacking TPH2, the main enzyme involved in the first step of serotonin synthesis in the brain.To tackle growth retardation, we monitored the pituitary activity of the pups at different ag

This study aims to evaluate the contribution of extraembryonic sources of serotonin to prefrontal cortex (PFC) development and understand the placental role and mechanisms of serotonin supplementation to the foetus. To this end, we used mice deficient in serotonin production (TPH1 and TPH2 KO) and serotonin transporters (SERT and OCT3 KO). We assessed serotonin levels in placenta and embryonic brain during different phases of prenatal neurodevelopment using HPLC and immunohistochemistry. Furthermore, we evaluated the PFC maturation and serotonergic wiring by 3D brain ECi imaging in these mice.

Tryptophan hydroxylase (TPH) is crucial for serotonin production, and TPH2 is primarily expressed in neurons. Human TPH2 variants are associated with major depressive, bipolar, and attention-deficit/hyperactivity disorders. Tph2 knockout (KO) in mice increases impulsivity and aggression. An imbalance in several transmitter systems, including serotoninergic signalling, also influences the process of medial prefrontal cortex (mPFC) development. The BALB/cJ mouse model with low serotonin shows altered distribution of Parvalbumin-positive (PV+) interneurons in the anterior cingulate (ACC) and midc

The prefrontal cortex (PFC) is responsible for higher cognitive tasks, and its ‘malfunction’ is shared across serotonin (5-HT)-related neuropsychiatric disorders and often find its origins during development. Proper cortical development is directed by a sequence of intrinsic ( transcription factors, local placental-derived 5-HT) and extrinsic (instructing 5-HT and catecholaminergic afferents) events. Recently, our group has shown a functional interplay between the 5-HT and catecholaminergic prefrontal projection systems during development leading to a distortion in PFC cytoarchitecture. Lack o