Changes in Corticotropin-Releasing Factor Receptor Type 1, Co-Expression with Tyrosine Hydroxylase and Oxytocin Neurons, and Anxiety-Like Behaviors across the Postpartum Period in Mice

Abstract

Introduction: Corticotropin-releasing factor and its primary receptor (CRFR1) are critical regulators of behavioral and neuroendocrine stress responses. CRFR1 has also been associated with stress-related behavioral changes in postpartum mice. Our previous studies indicate dynamic changes in CRFR1 levels and coupling of CRFR1 with tyrosine hydroxylase (TH) and oxytocin (OT) neurons in postpartum mice. In this study, we aimed to determine the time course of these changes during the postpartum period. Methods: Using a CRFR1-GFP reporter mouse line, we compared postpartum mice at five time points with nulliparous mice. We performed immunohistochemistry to assess changes in CRFR1 levels and changes in co-expression of TH/CRFR1-GFP and OT/CRFR1-GFP across the postpartum period. Mice were also assessed for behavioral stress responses in the open field test. Results: Relative to nulliparous mice, CRFR1 levels were elevated in the anteroventral periventricular nucleus (AVPV/PeN) but were decreased in the medial preoptic area from postpartum day 1 (P1) through P28. In the paraventricular hypothalamus (PVN), there is a transient decline in CRFR1 mid-postpartum with a nadir at P7. Co-localization of CRFR1 with TH-expressing neurons was also altered with a transient decrease found in the AVPV/PeN at P7 and P14. Co-expression of CRFR1 and OT neurons of the PVN and supraoptic nucleus was dramatically altered with virtually no co-expression found in nulliparous mice, but levels increased shortly after parturition and peaked near P21. A transient decrease in open field center time was found at P7, indicating elevated anxiety-like behavior. Conclusion: This study revealed various changes in CRFR1 across the postpartum period, which may contribute to stress-related behavior changes in postpartum mice.