Enduring neural and behavioral effects of early life adversity: Consequences of the absence of maternal melatonin and of neonatal hypoxia/anoxia

There is growing evidence that adversities at critical periods during early life, both pre- and postnatal, play an important role in determining the adult health status. On the base of these findings, the Developmental Origin of Adult Health and Disease (DOHaD) hypothesis was proposed, postulating that unfavorable environmental early-life conditions can result in “developmental programming” of later-life cardiovascular and metabolic diseases. In recent years, however, it became increasingly apparent that early-life adversity can also significantly affect brain development and may cause abnormal cognitive functioning and increase the vulnerability to neuropsychiatric disorders in adult life. Hence, the early life period and the maternal-fetal environment in particular arise as critical factors in determining later life consequences. The main objective of this thesis was to gain more insight into the biological processes at play during the programming of the brain by early-life adversities. By understanding how perinatal maternal and fetal environmental factors like the absence of maternal melatonin and the presence of neonatal hypo-/anoxia, can affect brain development and introduce lasting neuronal and behavioral effects. Specifically, we here studied the programming of hippocampal structure and function by in utero and post-natal early life adversities, while taking sex-specific vulnerabilities into account