Early-life oxytocin attenuates the social deficits induced by caesarean-section delivery in the mouse

Abstract

The oxytocin (OXT) system has been strongly implicated in the regulation of social behaviour and anxiety, potentially contributing to the aetiology of a wide range of neuropathologies. Birth by Caesarean-section (C-section) results in alterations in microbiota diversity in early-life, alterations in brain development and has recently been associated with long-term social and anxiety-like behaviour deficits. In this study, we assessed whether OXT intervention in the early postnatal period could reverse C-section-mediated effects on behaviour, and physiology in early life and adulthood. Following C-section or per vaginum birth, pups were administered with OXT (0.2 or 2 μg/20 μl; s.c.) or saline daily from postnatal days 1–5. We demonstrate that early postnatal OXT treatment has long-lasting effects reversing many of the effects of C-section on mouse behaviour and physiology. In early-life, high-dose OXT administration attenuated C-section-mediated maternal attachment impairments. In adulthood, low-dose OXT restored social memory deficits, some aspects of anxiety-like behaviour, and improved gastrointestinal transit. Furthermore, as a consequence of OXT intervention in early life, OXT plasma levels were increased in adulthood, and dysregulation of the immune response in C-section animals was attenuated by both doses of OXT treatment. These findings indicate that there is an early developmental window sensitive to manipulations of the OXT system that can prevent lifelong behavioural and physiological impairments associated with mode of birth.

Lasting consequences on physiology and social behavior following cesarean delivery in prairie voles

“…Similar to prior work examining the paraventricular nucleus of the hypothalamus in mice [48], we did not find evidence for substantial changes in OXTR and V1aR in the adult brains of CS offspring. Although we observed CS animals having greater OTR in the agranular insular cortex and claustrum, as well as CS females having greater OTR in the central amygdala, we must consider the large number of comparisons made.…”

“…While we observed no effect of CS on anxiety-like behavior in the OFT in the present study, the recent study by Morais and colleagues found that CS led to diminished anxiety-like (rather “repetitive”?) behavior in offspring mice, which could be prevent by OXT treatment [48]. CS mice also showed less preference for their natal nest, which was restored by treatment with the ∼1 mg/kg OXT dose.…”

Probiotic Interventions Alleviate Food Allergy Symptoms Correlated With Cesarean Section: A Murine Model

“…Instead of adding a cross-fostered group, we utilized vaginally born rats maintained by their biological moms as a control group because cross-fostering within the same strain has been shown to have little impact on bacterial communities (Shannon index, Chao index, and the relative abundance of the most predominant bacterial genera) or relative mRNA expression of immunoregulatory cytokines (TNFa, IFNg, IL-4, and IL-10) in the gastrointestinal tract of the offspring (63). Similarly, a non-cross-fostered control has been successfully implemented to investigate the deficits mediated by mode of delivery (11,64). Thus, for ethical reasons, we did not include extra groups in the current study to minimize animal usage.…”

“…Furthermore, a growing body of work has implicated CS in food allergy (2,3) and several other immune-mediated diseases, including asthma, inflammatory bowel disease, eczema, atopic dermatitis, and immune deficiencies (4)(5)(6)(7). CS in mice has also been shown to result in marked and long-term behavioral changes, regulatory immunity shifts, and increased sensitivity to oxazolone-induced colitis compared with mice delivered vaginally in offspring (8)(9)(10)(11).…”

From Short- to Long-Term Effects of C-Section Delivery on Microbiome Establishment and Host Health

“…Other strategies to recover behavioral deficits in murine models include treatment with oxytocin, which reverted some alterations in brain development, particularly the alterations related to social deficits; however, the study lacks information about the changes produced in the gut microbiome [63].…”