Gestational iron deficiency in depression-like behavior

The present project entitled Gestational iron deficiency in depression-like behavior is designed to investigate the consequences of insufficient supply of alimentary iron during pregnancy on offspring emotionality later in life. Iron deficiency (ID) is the most prevalent nutritional deficiency in the world. Iron is considered an essential element for numerous biological processes including brain development and function, evidencing the relevance and implications gestational iron deficiency (GID). During brain development, iron is essential for the myelination of white matter, orchestration of neuronal growth and arborization and the synthesis of elements of the monoaminergic neurotransmitter systems. ID in early life is therefore associated with alterations in neural development and related to behavioral and cognitive abnormalities with relevance for mental disorders. In the case of mood disorders, the association between ID and depression is well-established for ID in adulthood. However, the potential relevance of intra-uterine ID for the development of mood disorders later in life has not yet been investigated. In the current study we set-out to experimentally explore in the mouse model a possible effect of GID on offspring emotionality, focusing on the characterization of depression-like behaviors and the investigation of its neural underpinnings. To this end we aim to delineate the potential involvement of alterations in the midbrain dopaminergic system function and activity, given its relevance for the pathophysiology of depression and the documented impact of ID on dopaminergic neurotransmission. The dopamine system is also critically involved in the regulation of maternal care - a behavioral repertoire sensitive to environmental perturbations during pregnancy and an important modulator of offspring emotionality. Thus, we further strive to examine the relevance of maternal care behavior as mechanism contributing to and/or modifying the adult offspring behavioral phenotype. Hence, we here propose to test the following hypotheses: 1. GID modulates offspring emotional behavior related to depression; 2. GID affects maternal care behavior and alterations in maternal care modulate offspring behavior; 3. Enhanced depression-like behavior in offspring after GID is caused by alterations in the activity of dopaminergic neurons of the ventral tegmental area. The experimental approaches employed to evaluate the stated hypotheses will encompass a rich portfolio of state-of-the-arttechniquesincluding behavioral, in-vivo electrophysiological and optogenetic/pharmacogenetic approaches. Results obtained from the present research may shed first light onto the involvement of the most common gestational nutritional deficiency on an excruciating psychiatric disorder with highly significant socio-economic impact and lay the ground for future translational and clinical studies with the goal to improve preventative and therapeutic interventions.