Limited nesting stress in mice as a model to study neuroimmune relationships in postpartum depression

Postpartum depression (PPD) is a mood disorder that affects the ability of mothers to engage with and care for their infants. Stress exposure is known to be a major predisposing factor for PPD, while immune factors such as T regulatory cells (Tregs) are also hypothesized to influence the development of the disorder. Here we assessed limited nesting (LN) in mice, with or without depletion of Tregs through anti-CD25 antibody treatment, as a potential model to investigate the relationship between stress and the immune system in PPD. Dams and their pups were exposed to LN from post-natal day 3-10 and maternal behaviour was evaluated over this period followed by assessment of maternal self-care using the splash test. Gene expression in selected brain regions and the peripheral lymphocyte profile were also assessed. LN exposure led to a significant increase in aggressive behaviour towards the pups and altered grooming in the splash test. These effects on behaviour were associated with brain region specific changes in expression of several genes related to depression and maternal behaviour and with increased levels of Tregs in the periphery. When LN was combined with anti-CD25 antibody treatment, there were further deficits in nursing behaviour and changes in the brain circuitry related to lactation and stress. Our study indicates that LN in mice may be a useful model for studying neuroimmune relationships in certain aspects of PPD. Our data also suggest that post-partum regulatory immune changes may mitigate effects of stress on brain circuitry associated with maternal behaviour, lactation and stress.