Abstract
Postpartum depression is a complex illness that often occurs in genetically predisposed individuals. Closely related inbred rat strains are a great resource to identify novel causative genes and mechanisms underlying complex traits such as postpartum behavior. We report differences in these behaviors between the inbred depression model, Wistar Kyoto (WKY) More Immobile (WMI), and the isogenic control Wistar Kyoto Less Immobile (WLI) dams. WMI dams showed significantly lower litter survival rate and frequency of arched back and blanket nursing, but increased pup-directed licking, grooming, and retrieval during postpartum days (PPD) 1–10, compared to control WLIs. This increased pup-directed behavior and the frequency of self-directed behaviors segregated during selective breeding of the progenitor strain of WKY, which is also a depression model. These behaviors are manifested in the WMIs in contrast to those of WLIs. Furthermore, habitual differences in the self-directed behavior between light and dark cycles present in WLIs were missing in WMI dams. Hypothalamic transcript levels of the circadian rhythm-related gene Lysine Demethylase 5A (Kdm5a), period 2 (Per2), and the maternal behavior-related oxytocin receptor (Oxtr), vasopressin (Avp), and vasopressin receptor 1a (Avpr1a) were significantly greater in the post-weaning WMI dams at PPD 24 compared to those of WLIs, and also to those of WMI dams whose litter died before PPD 5. Expression correlation amongst genes differed in WLI and WMI dams and between the two time-points postpartum, suggesting genetic and litter-survival differences between these strains affect transcript levels. These data demonstrate that the genetically close, but behaviorally disparate WMI and WLI strains would be suitable for investigating the underlying genetic basis of postpartum behavior.
Highlights
Maternal behavior has long-term effects on the brain development of offspring, and depressive disorders impair maternal behaviors
The WMI genetic animal model of depression has shown major differences during postpartum compared to their isogenic controls, the Wistar Kyoto Less Immobile (WLI) strain that does not indicate depression-like behavior
Many of these characteristics segregated from the Wistar Kyoto (WKY) parent phenotype during selective breeding with most behavioral phenotypes of WMIs being the same as the WKYs, while WLIs being different
Summary
Maternal behavior has long-term effects on the brain development of offspring, and depressive disorders impair maternal behaviors. Postpartum Characteristics of Depression Model of postpartum depression focus on mirroring the group of women who are experiencing depression for the first time in their life during postpartum (Perani and Slattery, 2014; Putnam et al, 2017; Eid et al, 2019), the present study employs a genetic model of depression-like behavior and its isogenic control strain to begin to investigate characteristics of these dams during postpartum, modeling the risk factor of depression before pregnancy. The WKY rat strain is a well-established model for depression as its behavior mirrors symptoms of human major depression and anxiety, including despair-like behavior, excessive anxiety, learned helplessness, disturbed sleep patterns, and hypoactivity (Paré and Redei, 1993; Paré, 1994a,b; Dugovic et al, 2000; Redei et al, 2001; Solberg et al, 2001, 2004; Malkesman et al, 2005; Baum et al, 2006). Louis and Howes (Louis and Howes, 1990) demonstrated that the WKY strain was distributed to different vendors and universities between F12 and F17 generations of inbreeding
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