CRF binding protein activity in the hypothalamic paraventricular nucleus is essential for stress adaptations and normal maternal behaviour in lactating rats

• Published in: Neurobiology of stress 2024-05, Vol.30, p.100631-100631, Article 100631
• Main Authors: Sanson, Alice, Krieg, Paula, Schramm, Milena M., Kellner, Kerstin, Maloumby, Rodrigue, Klampfl, Stefanie M., Brunton, Paula J., Bosch, Oliver J.
• Format: Article
• Language: English
• Subjects: Corticotropin-releasing factor; CRF binding protein; Maternal behaviour; Original; PVN; Stress
• ISSN: 2352-2895; 2352-2895
• DOI: 10.1016/j.ynstr.2024.100631

To ensure the unrestricted expression of maternal behaviour peripartum, activity of the corticotropin-releasing factor (CRF) system needs to be minimised. CRF binding protein (CRF-BP) might be crucial for this adaptation, as its primary function is to sequester freely available CRF and urocortin1, thereby dampening CRF receptor (CRF-R) signalling. So far, the role of CRF-BP in the maternal brain has barely been studied, and a potential role in curtailing activation of the stress axis is unknown. We studied gene expression for CRF-BP and both CRF-R within the paraventricular nucleus (PVN) of the hypothalamus. In lactating rats, Crh-bp expression in the parvocellular PVN was significantly higher and Crh-r1 expression in the PVN significantly lower compared to virgin rats. Acute CRF-BP inhibition in the PVN with infusion of CRF(6–33) increased basal plasma corticosterone concentrations under unstressed conditions in dams. Furthermore, while acute intra-PVN infusion of CRF increased corticosterone secretion in virgin rats, it was ineffective in vehicle (VEH)-pre-treated lactating rats, probably due to a buffering effect of CRF-BP. Indeed, pre-treatment with CRF(6–33) reinstated a corticosterone response to CRF in lactating rats, highlighting the critical role of CRF-BP in maintaining attenuated stress reactivity in lactation. To our knowledge, this is the first study linking hypothalamic CRF-BP activity to hypothalamic-pituitary-adrenal axis regulation in lactation. In terms of behaviour, acute CRF-BP inhibition in the PVN under non-stress conditions reduced blanket nursing 60 min and licking/grooming 90 min after infusion compared to VEH-treated rats, while increasing maternal aggression towards an intruder. Lastly, chronic intra-PVN inhibition of CRF-BP strongly reduced maternal aggression, with modest effects on maternal motivation and care. Taken together, intact activity of the CRF-BP in the PVN during the postpartum period is essential for the dampened responsiveness of the stress axis, as well as for the full expression of appropriate maternal behaviour. [Display omitted] •CRF binding protein (CRF-BP) gene expression is increased in the PVN in lactation.•CRF-BP in the PVN limits basal activity of the HPA axis in lactation.•PVN CRF-BP is necessary for restraining stimulated HPA axis responses in lactation.•Acute and chronic CRF-BP inhibition have opposing effects on maternal aggression.