How Early Life Stress Impact Maternal Care: A Systematic Review of Rodent Studies

Abstract

Background: Maternal care refers to the behavior performed by the dam to nourish and protect her litter during its early development. Frequent and high-quality performance of such maternal behaviors is critical for the neurodevelopment of the pups. Maternal exposure to stress during early development can impair maternal care and amplify the deleterious effects of poor maternal caregiving and neglect. As such, a thorough understanding of the effects caused by several models of early life stress on maternal care may yield more insights into the relationship between stress and maternal behavior. Methods: A systematic review was performed to identify and address the effects of early life stress on maternal behavior. The search was conducted using three online databases: PUBMED, Embase, and Web of Science. To provide clear evidence of the impact of stress on maternal care, in every study, the stress group was always compared to a control group. Outcomes were categorized into eight different behaviors: (1) licking/grooming; (2) arched-back nursing; (3) blanket-nursing/passive nursing; (4) nest building; (5) contact with pups; (6) harmful/adverse caregiving; (7) no contact; (8) nest exits. Additionally, the methodological quality of the studies was evaluated. Results: A total of 12 different early life stress protocols were identified from the 56 studies included in this systematic review. Our data demonstrate that different stress models can promote specific maternal patterns of behavior. Regarding the maternal separation protocol, we observed an overall increase in nursing and licking/grooming behaviors, which are essential for pup development. An increase in the number of nest exits, which represents a fragmentation of maternal care, was observed in the limited bedding protocol, but the total amount of maternal care appears to remain similar between groups. Conclusions: Each stress protocol has unique characteristics that increase the difficulty of rendering comparisons of maternal behavior. The increase in maternal care observed in the maternal separation protocol may be an attempt to overcompensate for the time off-nest. Fragmented maternal care is a key component of the limited bedding protocol. Moreover, the methodological approaches to evaluate maternal behavior, such as time, duration, and behavior type should be more homogeneous across studies.

Maternal Separation Combined With Limited Bedding Increases Anxiety-Like Behavior and Alters Hypothalamic-Pituitary-Adrenal Axis Function of Male BALB/cJ Mice

“…However, during the MS paradigm, the threat tends to raise in response to the novel environment. On the other hand, in a recent review from our laboratory (Orso et al, 2019), we found that MS alone induces an increase in the levels of licking/grooming post-reunion. This counterbalance behavior (increase in maternal care) could attenuate the deprivation characteristics of the MS model, and possibly minimize the effects of the separation period (Davis et al, 2020;Wang et al, 2020).…”

Chemogenetic manipulation of the bed nucleus of the stria terminalis counteracts social behavioral deficits induced by early life stress in C57BL/6J mice

“…Mice in the present study were exposed only to same-sex conspecifics, and many studies reporting sex differences in BNST-mediated behaviors attribute differences to mating or mating-related behaviors (Maejima, Ohishi, Yamaguchi, & Tsukahara, 2015;Wersinger, Baum, & Erskine, 1993), so it is possible that sex differences may have emerged here had we exposed mice to conspecifics of the opposite sex. Also of note, the majority of past mouse studies examining ELS effects have excluded females entirely or neglected to report comparisons between sexes (see Orso et al, 2019), so it is difficult to compare the reported frequency of BNST behavior-related sex differences in the literature to the present findings.…”

“…To understand how ELS alters neurobiology in a way that promotes such aberrant behavior, many studies have used rodent models of maternal separation in which early postnatal pups are deprived of necessary maternal care by separating them from the dam for extended periods of time (for reviews see Nishi, Horii-Hayashi, & Sasagawa, 2014;Orso et al, 2019;Tractenberg et al, 2016). Rodent maternal separation during the early postnatal period has been shown to produce an array of adolescent and adulthood behavioral effects not limited to increased anxiety-like behavior (Caldji, Diorio, & Meaney, 2000;Daniels, Pietersen, Carstens, & Stein, 2004;Lee et al, 2007;Levine, 1967;Liu, Diorio, Day, Francis, & Meaney, 2000;Matthews, Hall, Wilkinson, & Robbins, 1996), hyper-responsiveness to stressors (Holmes et al, 2005;Meaney, 2001;Ogawa et al, 1994;Plotsky & Meaney, 1993), altered reward learning and cognition (Forster, Anderson, Scholl, Lukkes, & Watt, 2018;Liu et al, 2000;Matthews & Robbins, 2003;Portero-Tresserra et al, 2018;Pryce, Bettschen, Nanz-Bahr, & Feldon, 2003;Sasagawa et al, 2017), deviations in normal fear learning and memory (Callaghan, Graham, Li, & Richardson, 2013;Chocyk et al, 2014), and deficits in social behavior (Frank et al, 2019;Kompier, Keysers, Gazzola, Lucassen, & Krugers, 2019;Venerosi, Cirulli, Capone, & Alleva, 2003;Wang et al, 2017).…”

Systematic review and meta-analysis: effects of maternal separation on anxiety-like behavior in rodents

“…Given the important role that maternal behaviors such as licking and grooming (LG) or arched-back nursing (ABN) play in the development of circuits that regulate defensive-exploratory behavior 23 it is important to consider the effects of MS on these behaviors in rats and mice. This issue was recently reviewed by Orso et al who found that MS induces higher levels of LG-ABN in rats compared to mice 46 . This increase in maternal behavior would expect to minimize and not to exacerbate the consequences of MS in rats.…”