A novel antibody that neutralizes corticotropin-releasing factor attenuates the cardiovascular effects of chronic social defeat stress in mice

Abstract

According to the World Health Organization, cardiovascular disease (CVD) continues to be the leading cause of death worldwide. While a myriad of genetic and environmental factors influence the development of CVD, there are several lines of evidence suggesting that psychological stress contributes to health disparities in CVD observed amongst different populations. Our lab seeks to understand the effects of psychosocial stress on cardiovascular health using a model of chronic social defeat stress (CSDS) in mice. In this paradigm, male C57BL/6 mice undergo brief daily defeat sessions and are housed in the same cage as the larger, more aggressive CD1 defeater mouse, separated by a polycarbonate divider that allows for continuous visual, auditory, and olfactory contact while preventing physical contact. We have previously demonstrated that this paradigm causes robust and persistent elevations in blood pressure, indices of chronic inflammation, elevations in plasma corticosterone and cardiac and adrenal hypertrophy. Social defeat also leads to robust activation of corticotropin releasing factor (CRF) neurons within the paraventricular nucleus of the hypothalamus (PVN). In the present studies, we investigate whether we can alleviate some of the adverse effects of CSDS through targeting the HPA axis using CTRND05, a novel anti-CRF antibody. Adult male C57BL/6 mice were assigned to either CSDS or control (paired) housing. Following 14 days of CSDS or control housing, mice were treated with one injection of CTRND05 (25 mg/kg, i.p.) or vehicle (IgG), followed by 14 more days of CSDS or control housing. A booster administration of CTRND05 (12.5 mg/kg, i.p.) was given 7 days after the initial dose. Adrenal weights were significantly reduced in pair housed mice treated with CTRND05 compared to pair housed mice treated with IgG, and there was a trend towards a reduction in adrenal weight of CSDS mice treated with CTRND05 in comparison with CSDS mice treated with IgG. There was also a trend for reduced basal corticosterone in CSDS mice treated with CTRND05. Importantly, while IgG treatment had no effect on the systolic blood pressure (SBP) of CSDS mice, treatment with CTRND05 significantly lowered the SBP of CSDS mice when compared with pre-treatment. These data suggest that targeting CRF may serve as a therapeutic tactic for treatment of stress-related hypertension. R35HL150750, R01HL136595. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.