Lopez, J.-P. | bioRxiv Science

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↗

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↗