Adult hippocampal neurogenesis-mediated cognitive behavior participates in stress resilience to anxiety and depression-like behaviors in postpartum dams

Postpartum period being a critical phase affecting women’s health recovery, and stressful events during this period are major risk factors for postpartum depression. Pup separation (PS) serves as a natural model of postpartum maternal care. However, the effects of different PS (no separation, NPS; 15 min/day, PS15, brief PS; 180 min/day, PS180, long PS) during lactation on stress-induced behavioral deficits in dams, along with the underlying mechanisms of resilience remain unclear. In this study, we assessed cognitive and emotional behaviors in lactating C57BL/6 J dams subjected to different PS from postnatal day 1 to day 21, along with chronic restraint stress (CRS). Subsequently, hippocampal samples were collected to analyze the expression of NLRP3, IL-18, and IL-1β, along with microglial activation and adult hippocampal neurogenesis (AHN) in the hippocampal dentate gyrus. We further modulated AHN using viral and examined the effects of AHN overexpression or inhibition on behavior and hippocampal neuroinflammation. Dams subjected to brief PS exhibited reduced anxiety and depressive-like behaviors and improved cognitive function. Additionally, PS15 dams showed decreased hippocampal expression of NLRP3, IL-18, and IL-1β, reduced microglia activation, and increased AHN. Overexpression of AHN can significantly improved cognitive function, but no significant changes in emotional behaviors were observed. Besides, AHN-mediated cognitive behavior participates in resilience to anxiety and depression-like behaviors of dams after CRS. Similarly, inhibition of hippocampal NLRP3 expression enhanced AHN-related cognitive behavior and promoted stress resilience in adult female mice. Brief PS resulted in resilience to anxiety and depressive-like behaviors in dams and mitigated memory impairments induced by CRS. This study confirmed AHN-mediated cognitive behavior participates in stress resilience to anxiety and depression-like behaviors in postpartum dams after CRS.