Abstract
Recent studies support the hypothesis that the adverse effects of early-life adversity and transgenerational stress on neural plasticity and behavior are mediated by inflammation. The objective of the present study was to investigate the immune and behavioral programing effects of intranasal (IN) vasopressin (AVP) and oxytocin (OXT) treatment of chronic social stress (CSS)-exposed F1 dams on F2 juvenile female offspring. It was hypothesized that maternal AVP and OXT treatment would have preventative effects on social stress-induced deficits in offspring anxiety and social behavior and that these effects would be associated with changes in interferon-γ (IFNγ). Control and CSS-exposed F1 dams were administered IN saline, AVP, or OXT during lactation and the F2 juvenile female offspring were assessed for basal plasma IFNγ and perseverative, anxiety, and social behavior. CSS F2 female juvenile offspring had elevated IFNγ levels and exhibited increased repetitive/perseverative and anxiety behaviors and deficits in social behavior. These effects were modulated by AVP and OXT in a context- and behavior-dependent manner, with OXT exhibiting preventative effects on repetitive and anxiety behaviors and AVP possessing preventative effects on social behavior deficits and anxiety. Basal IFNγ levels were elevated in the F2 offspring of OXT-treated F1 dams, but IFNγ was not correlated with the behavioral effects. These results support the hypothesis that maternal AVP and OXT treatment have context- and behavior-specific effects on peripheral IFNγ levels and perseverative, anxiety, and social behaviors in the female offspring of early-life social stress-exposed dams. Both maternal AVP and OXT are effective at preventing social stress-induced increases in self-directed measures of anxiety, and AVP is particularly effective at preventing impairments in overall social contact. OXT is specifically effective at preventing repetitive/perseverative behaviors, yet is ineffective at preventing deficits in overall social behavior.
Highlights
Alterations in maternal care can mediate the developmental consequences of early-life experiences
There were no significant differences in marble burying following one-way ANOVA (F4,38 = 1.5, p = 0.2, F3,38 = 1.5, p = 0.2, Figure 2 | Mean + SEM of basal IFNγ levels of chronic social stress (CSS) F2 juvenile female offspring of F1 control (CON) or CSS dams intranasally treated with saline, vasopressin, or oxytocin. # indicates overall effect of CSS treatment, * indicates significant increase compared to combined CON and control + intranasal saline (CON SAL) groups and CON SAL alone (p < 0.05)
Ongoing studies of the CSS model will explore the role of maternal care in the effects of IN AVP and OXT on offspring behavior and immune function. These results support the hypothesis that maternal AVP and OXT treatment have context- and behavior-specific effects on peripheral IFNγ levels and perseverative, anxiety, and social behaviors in female offspring of early-life social stressexposed dams
Summary
Alterations in maternal care can mediate the developmental consequences of early-life experiences. Maternal–infant interactions serve as a potential source of information concerning the environment to which offspring will need to adapt. Levels of maternal care can profoundly influence stress physiology in the infant and their developmental trajectory [1]. Further studies have shown that alterations in maternal care can be nongenomically inherited. Wild-type offspring born to a mother mutant for the Peg3þ/(paternally expressed gene 3) gene, which shows impairments in various aspects of maternal behavior, exhibited a reduction in their own ability to retrieve pups to a nest in a retrieval test [3]. We have demonstrated that chronic social stress (CSS) can alter levels of maternal care behavior and associated neuroendocrine changes in offspring [4, 5]
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