Chronic gestational stress leads to depressive-like behavior and compromises medial prefrontal cortex structure and function during the postpartum period.

Postpartum depression, which affects approximately 15% of new mothers, is associated with impaired mother-infant interactions and deficits in cognitive function. Exposure to stress during pregnancy is a major risk factor for postpartum depression. However, little is known about the neural consequences of gestational stress. The medial prefrontal cortex (mPFC) is a brain region that has been linked to stress, cognition, maternal care, and mood disorders including postpartum depression. Here we examined the effects of chronic gestational stress on mPFC function and whether these effects might be linked to structural modifications in the mPFC. We found that in postpartum rats, chronic gestational stress resulted in maternal care deficits, increased depressive-like behavior, and impaired performance on an attentional set shifting task that relies on the mPFC. Furthermore, exposure to chronic stress during pregnancy reduced dendritic spine density on mPFC pyramidal neurons and altered spine morphology. Taken together, these findings suggest that pregnancy stress may contribute to postpartum mental illness and its associated symptoms by compromising structural plasticity in the mPFC

Chronic gestational stress impairs cognitive flexibility.

<p>Compared to postpartum females who were unstressed, postpartum females stressed in pregnancy showed impairments on the reversal (REV) and extra dimensional (EDS) phases of the attentional set shifting task as demonstrated by more trials (a) and errors (b) to reach criterion. The number of trials (a) and errors (b) to reach criterion for the simple discrimination (SD), compound discrimination (CD) and intradimensional shift (IDS) did not differ between unstressed and stressed mothers. Bars represent mean ± SEM, * <i>p</i><0.05.</p

Behavioral protocol for attentional set shifting.

<p>Representative example of stimulus pairs and the progression through stages of the attentional set shifting task. Digging medium was the initial discriminative stimulus dimension, shifting to texture in the EDS stage. For each stage, the positive stimulus is in bold and is paired randomly across trials with the two stimuli from the irrelevant dimension.</p

Chronic gestational stress impairs postpartum maternal care.

<p>Exposure to chronic stress during pregnancy increased the percentage of time postpartum females spent away from the nest (a) and reduced arched-back nursing (b). Bars represent mean ± SEM, * <i>p</i><0.05.</p

Chronic gestational stress increases postpartum depressive-like, but not anxiety-like, behaviors.

<p>Exposure to chronic stress during pregnancy increased the percentage of time postpartum females spent immobile in the forced swim test (a). Chronic gestational stress did not alter anxiety-like behavior in the elevated plus maze. Stressed and unstressed mothers spent a similar percentage of time (b) and made a similar number of entries (c) into the open arms. Locomotor activity, as assessed by closed arms entries in the EPM (d), was unaffected by gestational stress. Bars represent mean ± SEM, * <i>p</i><0.05.</p

Chronic gestational reduces mPFC dendritic spine density and alters spine morphology.

<p>Postpartum females subjected to chronic gestational stress had fewer dendritic spines on apical and basal dendrites of layer 2/3 pyramidal neurons in the mPFC (a). Representative DiI labeled dendritic segments, scale bar = 1 µm (b). Exposure to chronic gestational stress also caused a shift in spine morphology such that there was a decrease in the proportion of thin spines but an increase in the proportion of mushroom spines in stressed mothers (c). Bars represent mean ± SEM, * <i>p</i><0.05.</p