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Title: Limited nesting in mice as a model to study the psychoneuroimmunology of post-partum depression
Supervisor: Forsythe, Paul
Authors: Marie Armbruster, Ritu Mann-Nuttel, Shivani Mandal, Paul Forsythe
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Funded by This study was funded in part by BioGaia AB (Sweden)
Introduction: Postpartum depression (PPD) is a common mood disorder that typically develops within 6 months following delivery and concerns 10 to 15% of women. The major symptoms include mood swings, anxiety, anhedonia and disinterest in the baby. Some mothers suffering from PPD also demonstrate increased aggression and harm towards their infants. The disease affects not only the mother's well-being but also her ability to engage with and care for their infant, resulting in impaired cognitive and social development for their children. Stress exposure during the postpartum period is a major predisposing factor for PPD, while immune factors such as T regulatory cells (Tregs) are also hypothesised to influence the development of the disorder. Here we assessed limited nesting (LN) in mice as a potential model to investigate the relationship between stress and the immune system in PPD.
Methods: C57BL6J mice and their pups were provided limited nesting material from post-natal day 3-10 while controls had standard cages. Tregs were depleted with anti-CD25 antibody injections on post-natal day 2. Maternal behaviour was observed every day over the LN period followed by an assessment of depressive-like behaviour using the splash test. Gene expression in selected brain regions was determined using qRT-PCR and the immune profile of splenocytes was characterised using FACS.
Results: Postnatal LN exposure led to a significant increase in negative maternal behaviour and signs of stress in dams, including food 'nibbling'. However, the behaviour in the splash test was not altered. In response to the LN, BDNF expression was reduced in the prefrontal cortex (PFC) while oxytocin and corticotropin-releasing hormone expressions were increased in the hypothalamus. LN was also associated with significantly decreased pups' weights. A combination of LN and Treg depletion significantly reduced the active nursing by dams which was associated with enhanced expression of vasopressin, vasopressin receptor, oxytocin receptor and prolactin receptor in the hypothalamus.
Conclusion: LN modelled some aspects of PPD behaviour including increased aggression towards offspring, with an associated reduction in BDNF expression in the PFC. BDNF is involved in neuronal growth, synapse formation, and plasticity and decreased levels of BDNF have been associated with PPD. However, LN did not alter self-care behaviour as determined in the splash test. Depletion of Treg enhanced the effect of LN on the maternal brain and behaviour decreasing active nursing and altering the expression of genes associated with maternal bond, maternal aggression and lactation. Our data suggests that, in the post-partum period, regulatory immune changes may mitigate the effects of stress on brain circuitry associated with maternal behaviour. Our study also indicates that LN in mice may be a useful model for studying the neuroimmune relationships in certain aspects of PPD.​