Investigation of Sex Differences in Hypothalamic Reelin and its Implications on Stress- Related Pathology




Liria Sánchez-Lafuente, Carla

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Women are twice more likely to suffer from stress-related disorders like depression. In addition, when depression occurs during the post-partum period, it can have detrimental effects on the child. Advances in the understanding of the neurobiology of stress and pathophysiology of depression have suggested an important role for biological sex differences, yet most preclinical studies investigating new therapeutic avenues have focused mostly on males. Persistent rises in glucocorticoids due to chronic stress can lead to maladaptive states and cause alterations in proteins such as reelin. Previous studies have observed that chronic stress induced with corticosterone causes decreases in reelin that parallel the development of depressive-like behaviours in rats. Reelin modulates neural plasticity in the adult brain and alterations in its levels have been observed in depressed patients. Moreover, reelin deficiency confers vulnerability to stress while overexpression or increased levels accomplished through central and peripheral administration restores stress-induced behavioural and neurochemical alterations. In this dissertation I present novel evidence towards sexually dimorphic reelin populations in the brain in key regulatory areas of the stress response that are differentially affected by chronic stress induced with corticosterone in rats. Moreover, I show preliminary evidence towards novel antidepressant-like effects of peripheral reelin in females during the post-partum period. By providing further evidence towards biological sex-differences in the brain that might contribute to stress-dysregulation and development of depression, this dissertation addresses a critical research gap that will help increase translatability of scientific findings from bench to bedside.



Reelin, Depression, sex differences, hypothalamus, animal model