engleski

Prenatal Programming of Altered Serotonin Functioning: Maternal Gestational Diabetes, Obesity and Emotional Stress as Potential Risk Factors

Serotonin (5HT) is a modulatory neurotransmitter involved in the fine-tuning of numerous brain functions, ranging from mood, sleep and appetite regulation to sensory perception and cognition. Many mental health and metabolic conditions have been linked to disturbed 5HT signalling, and the pharmacological targeting of 5HT-regulating proteins is extensively used in their treatment. Yet, causes of 5HT disturbances are poorly understood. Prior to assuming its neurotransmitter functions in the adult brain, 5HT plays crucial roles in the regulation of brain development, influencing proper genesis, differentiation and maturation of its own neurons and their target regions. In early stages of neurodevelopment, the placenta plays an important role in supplying the developing brain with serotonin. Hence, placental 5HT homeostasis emerges as a critical determinant of proper neurodevelopment. In order to better understand developmental origins of altered 5HT functioning, we have established a cross- disciplinary longitudinal study aimed at investigating the relationships between specific prenatal adversities, molecular indicators of placental / neonatal 5HT system functioning and the developmental outcomes in infancy. In particular, we hypothesize that the intrauterine environment associated with maternal emotional stress, obesity or gestational diabetes, known risk factors for behavioural and metabolic disorders in the offspring, may affect placental and fetal 5HT homeostasis through epigenetic mechanisms such as changes in DNA methylation pattern. Here we will outline the study design, present our preliminary findings on the expression and DNA methylation of several 5HT-regulating genes in placentas obtained from pregnancies complicated by maternal obesity and/or gestational diabetes, and discuss their potential implications for developmental programming of 5HT-related disorders.

Prenatal Development ; Serotonin ; Brain Disorders ; Neuroplacentology - 98

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