Biology subjects

Brivio, E.

Publications and source records attributed to Brivio, E..

3 recordsLinked to original sources

bioRxiv2020

Hypothalamic glucocorticoid receptor in CRF neurons is essential for HPA axis habituation to repeated stressor

Short abstractHabituation of the hypothalamic-pituitary-adrenal (HPA) axis to repeated homotypic stressors is crucial for the organisms well-being. Many physiological and psychological disorders are associated with HPA axis dysfunction. Here, we show that glucocorticoid receptors in CRF neurons of the hypothalamic paraventricular nucleus are essential for HPA habituation. By increasing inhibitory tone onto CRF neurons, glucocorticoid receptors led to essential cellular modulation and hypothalamic-pituitary-adrenal axis activation dampening, when re-exposed to the same stressor.

neuroscience↗

bioRxiv2020

Sexually divergent effects of social dominance on chronic stress outcomes in mice

BackgroundSex and social context are two major factors in the development of depression and other stress-related disorders. However, few studies of the effects of stress on rodent behavior and physiology have investigated social context and fewer still have assessed the possibility of sex-specific effects of social context. MethodsWe assessed social dominance of group-living mice during several days of monitoring using a high-throughput automated behavioral tracking system. We then exposed groups from each sex to a three-week chronic mild stress (CMS) procedure, followed by a behavioral test battery. Finally, we used principle component analysis and post-hoc tests to explore the sources of variance in the behavioral outcome data. ResultsWe found stable hierarchies in both sexes, however social dominance in males exhibited several additional associations with behaviors related to locomotion and exploration that were not seen in females. Crucially, pre-stress social dominance status was associated with opposing outcomes on multiple behavioral readouts between the two sexes following CMS. In particular, subordinate male mice and dominant female mice appeared more responsive to the environmental challenge, as observed in anxiety-like and locomotor behaviors. ConclusionsThis work demonstrates that sex differences interact with preexisting social dominance status to alter the effects of chronic stress. It highlights the importance of understanding the interplay between sex and social context and its contribution to individual differences in stress response.

neuroscience↗

bioRxiv2019

The co-chaperone Fkbp5 shapes the acute stress response in the paraventricular nucleus of the hypothalamus

Disturbed activation or regulation of the stress response through the hypothalamic-pituitary-adrenal (HPA) axis is a fundamental component of multiple stress-related diseases, including psychiatric, metabolic and immune disorders. The FK506 binding protein 51 (FKBP5) is a negative regulator of the glucocorticoid receptor (GR), a main driver of HPA axis regulation, and FKBP5 polymorphisms have been repeatedly linked to stress-related disorders in humans. However, the specific role of Fkbp5 in the paraventricular nucleus of the hypothalamus (PVN) in shaping HPA axis (re)activity remains to be elucidated. Using deletion, overexpression, and rescue of Fkbp5 exclusively in the PVN, we establish the fundamental importance of Fkbp5 in the HPA axis stress response. Furthermore, we show that Fkbp5 manipulation alters GR activation and elucidate the cellular complexity in the PVN, in which Fkbp5 operates.

neuroscience↗