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

Sanson, Alice and Krieg, Paula and Schramm, Milena M. and Kellner, Kerstin and Maloumby, Rodrigue and Klampfl, Stefanie M. and Brunton, Paula J. and Bosch, Oliver J. (2024) CRF binding protein activity in the hypothalamic paraventricular nucleus is essential for stress adaptations and normal maternal behaviour in lactating rats. NEUROBIOLOGY OF STRESS, 30: 100631. ISSN 2352-2895,

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Abstract

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 (CRFR) 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.

Item Type: Article
Uncontrolled Keywords: CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; MESSENGER-RNA EXPRESSION; NEUROENDOCRINE RESPONSES; STRIA TERMINALIS; SEX-DIFFERENCES; BED NUCLEUS; HPA AXIS; OXYTOCIN; HORMONE; Corticotropin-releasing factor; CRF binding protein; Maternal behaviour; PVN; Stress
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Zoologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 16 Jul 2025 06:25
Last Modified: 16 Jul 2025 06:25
URI: https://pred.uni-regensburg.de/id/eprint/63519

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