Lifespan psychomotor behaviour profiles of multigenerational prenatal stress and artificial food dye effects in rats

Sherpa Romeo green journal, open accessThe consumption of artificial food dye (AFD) during childhood and adolescence has been linked to behavioural changes, such as hyperactivity. It is possible that the vulnerability to AFDs is modified by prenatal stress. Common consequences of prenatal stress include hyperactivity, thus potentially leading to synergistic actions with AFDs. Here, we investigated the compounding effect of multigenerational prenatal stress (MPS) and AFD consumption on the development of hyperactivity and anxiety-related behaviours across the lifespan in male rats. MPS treatment involved a family history of four consecutive generations of prenatal stress (F4 generation). AFD treatment included a 4%-concentration of FD&C Red 40, FD&C Yellow 5, FD&C Yellow 6, and FD&C Blue 1 in the drinking water from postnatal days 22 to 50 to resemble juvenile and adolescent dietary exposure. Using several exploration tasks, animals were tested in motor activity and anxiety-like behaviours from adolescence to 13 months of age. MPS resulted in hyperactivity both early (50 days) and later in life (13 months), with normalized activity patterns at reproductive age. AFD consumption resulted in hyperactivity during consumption, which subsided following termination of treatment. Notably, both MPS and AFD promoted risk-taking behaviour in young adults (3 months). There were few synergistic effects between MPS and AFD in this study. The findings suggest that AFDs exert the most noticeable effects at the time of exposure. MPS, however, results in a characteristic lifespan profile of behavioural changes, indicating that development and aging represent particularly vulnerable periods in life during which a family history of prenatal stress may precipitate.Ye

Transgenerational programming of maternal behaviour by prenatal stress

Sherpa Romeo green journal. Open access, distributed under the terms of the Creative Commons Attribution (CC-BY) LicensePeripartum events hold the potential to have dramatic effects in the programming of physiology and behaviour of offspring and possibly subsequent generations. Here we have characterized transgenerational changes in rat maternal behaviour as a function of gestational and prenatal stress. Pregnant dams of the parental generation were exposed to stress from days 12-18 (F0-S). Their daughters and grand-daughters were either stressed (F1-SS, F2-SSS) or non-stressed (F1-SN, F2-SNN). Maternal antepartum behaviours were analyzed at a time when pregnant dams usually show a high frequency of tail chasing behaviours. F1-SS, F2-SNN and F2-SSS groups showed a significant reduction in tail chasing behaviours when compared with controls. The effects of multigenerational stress (SSS) slightly exceeded those of transgenerational stress (SNN) and resulted in absence of tail chasing behaviour. These findings suggest that antepartum maternal behaviour in rats is programmed by transgenerational inheritance of stress responses. Thus, altered antepartum maternal behaviour may serve as an indicator of an activated stress response during gestation.Ye

Sin Nombre Virus and Rodent Species Diversity: A Test of the Dilution and Amplification Hypotheses

BACKGROUND:Species diversity is proposed to greatly impact the prevalence of pathogens. Two predominant hypotheses, the "Dilution Effect" and the "Amplification Effect", predict divergent outcomes with respect to the impact of species diversity. The Dilution Effect predicts that pathogen prevalence will be negatively correlated with increased species diversity, while the Amplification Effect predicts that pathogen prevalence will be positively correlated with diversity. For many host-pathogen systems, the relationship between diversity and pathogen prevalence has not be empirically examined. METHODOLOGY/PRINCIPAL FINDINGS:We tested the Dilution and Amplification Effect hypotheses by examining the prevalence of Sin Nombre virus (SNV) with respect to diversity of the nocturnal rodent community. SNV is directly transmitted primarily between deer mice (Peromyscus maniculatus). Using mark-recapture sampling in the Spring and Fall of 2003-2005, we measured SNV prevalence in deer mice at 16 landscape level sites (3.1 hectares each) that varied in rodent species diversity. We explored several mechanisms by which species diversity may affect SNV prevalence, including reduced host density, reduced host persistence, the presence of secondary reservoirs and community composition. We found a negative relationship between species diversity and SNV prevalence in deer mice, thereby supporting the Dilution Effect hypothesis. Deer mouse density and persistence were lower at sites with greater species diversity; however, only deer mouse persistence was positively correlated with SNV prevalence. Pinyon mice (P. truei) may serve as dilution agents, having a negative effect on prevalence, while kangaroo rats (Dipodomys ordii), may have a positive effect on the prevalence of SNV, perhaps through effects on deer mouse behavior. CONCLUSIONS/SIGNIFICANCE:While previous studies on host-pathogen systems have found patterns of diversity consistent with either the Dilution or Amplification Effects, the mechanisms by which species diversity influences prevalence have not been investigated. Our study indicates that changes in host persistence, coupled with interspecific interactions, are important mechanisms through which diversity may influence patterns of pathogens. Our results reveal the complexity of rodent community interactions with respect to SNV dynamics

A lifespan profile of the effect of artificial food dye consumption on motor activity in the open field task.

<p>(A) AFD consumption (n = 16) from postnatal days 22 through 50 did not increase the mean distance travelled when compared to untreated animals (n = 16). (B) AFD consumption (n = 16) resulted in an increase in the mean movement time while the animals were placed on the AFD-containing diet when compared to untreated animals (n = 16). However, these effects were not found after the AFD was removed from the diet. Asterisks indicate significances: * p<0.05, compared to untreated animals.</p

A lifespan profile of the effect of multigenerational prenatal stress on motor activity in the open field task.

<p>(A) Multigenerational prenatal stress (n = 16) resulted in a significant increase in the mean distance travelled at 1.5 months and 13 months of age, but not at 3 or 7 months of age, when compared to non-stress animals (n = 16). (B) Multigenerational prenatal stress (n = 16) resulted in a significant increase in mean movement time at 1.5 months and 13 months of age, but not at 3 or 7 months of age, when compared to non-stress animals (n = 16). Thus, motor activity of MPS rats resembles that of non-stressed rats during peak sexual reproductive age, but differs early in life and in late adulthood. Asterisks indicate significances: * p<0.05; ** p<0.01, compared to non-stress animals.</p

Experimental design.

<p>The present study used male rats in a two-by-two factorial design. The independent variables were multigenerational prenatal stress and artificial food dye (AFD) consumption. The multigenerational prenatally stressed rats were the fourth generation (F4) of a familial line in which dams in each generation were given stress during pregnancy. Both the stressed and non-stressed animals were given either normal tap water or a 4%-AFD solution for regular consumption.</p

Behavioural effects of multigenerational prenatal stress and artificial food dye consumption in the affective exploration task.

<p>(A) At both 1.5 and 13 months of age, there were no effects of treatment with regard to the latency to emerge from the refuge. However, at 3 months of age, AFD-only animals (n = 8) were less reluctant to exit the refuge than any other group (n = 8 per group). (B) At 3 months of age, the AFD-only group (n = 8) was the fastest to exit the safe refuge. (C) Percentage of animals in each group that left the safe refuge at the age of 3 months. Both the prenatally stressed and AFD-treated groups left the refuge in 100% (n = 8) of the test sessions, while both control and combined prenatal stress and AFD groups left the safe refuge only in 62% of the time (n = 5 out of n = 8). Asterisks indicate significances: * p<0.05; ** p<0.01, compared to controls.</p

Multiple prenatal stresses increase sexual dimorphism in adult offspring behavior

Introduction: Maternal gestational stress and immune activation have independently been associated with affective and neurodevelopmental disorders across the lifespan. We investigated whether rats exposed to prenatal maternal stressors (PNMS) consisting of psychological stress, interleukin (IL)-1 beta or both (two-hit stress) during critical developmental windows displayed a behavioral phenotype representative of these conditions. Methods: Long-Evans dams were exposed to psychological stressors consisting of restraint stress and forced swimming from gestational day (GD)12 to 18 or to no stress (controls). From GD17 until day of delivery, these same animals were injected with saline or IL-1 beta as a second hit and immune stressor (5 mu g/day, intraperitoneally). The behavior of F1 offspring adults was tested on the open field test, elevated plus maze and affective exploration task on postnatal days (P)90, 100 and 110 respectively. Results: The effects of PNMS differed depending on the specific testing environment and potentially the age at assessment, especially in female offspring. Both locomotion and anxiety-like behavioral measures were susceptible to PNMS effects. In females, psychological stress increased anxiety-like behavior, whereas IL-1 beta had an opposite effect, inducing exploration and risk-taking behavior on the open field test and the elevated plus maze. When present, interactions between both stressors limited the anxiogenic effect of psychological stress on its own. In contrast, prenatal psychological stress increased anxiety-like behavior in adult males overall. A similar anxiogenic effect of IL-1 beta was only found on the open field test while the Stress*IL-1 beta interaction appeared to limit the effect of either alone. Contrarily, the PNMS effects on anxiety-like behavior on the affective exploration task were highly similar between both sexes. Analysis of males and females together revealed an additive effect of Stress and IL-1 beta on the number of exits from the refuge, a measure of risk assessment and thus correlated with anxiety. Conclusion: PNMS affected offspring adult behavior in a sex-dependent manner. Effects on females were more variable, whereas psychological stress mostly induced anxiety-like behavior in males. These data highlight the sexual dimorphism in vulnerability to prenatal stressors. Maternal or stress-induced programming of the stress response and neuroinflammation may play an important role in mediating stress effects on offspring adult behavior

Social Isolation Stress Modulates Pregnancy Outcomes and the Inflammatory Profile of Rat Uterus

Prenatal stressors have been linked to adverse pregnancy outcomes; including preterm birth (PTB). Recent work demonstrates that social isolation in mothers represents a silent stressor contributing to PTB risk. Here; we investigate the association of inflammatory and stress markers with PTB risk in Long–Evans rats exposed to social isolation stress (SIS) during preconception and pregnancy across four generations (F0-F3). Gestational length; blood glucose; corticosterone levels; and maternal and offspring weights were assessed in two SIS paradigms: transgenerational (TG) and multigenerational (MG) exposure. Maternal uterine tissues were collected 21 days after the dams gave birth. Exposure to SIS reduced pregnancy lengths in the parental generation and neonatal birth weights in the F1 and F2 generations. Interleukin (IL)-1β (Il1b) mRNA levels increased in F0 animals but decreased in the offspring of both stress lineages. Protein levels of IL-1β decreased in the TG lineage. Corticotrophin-releasing hormone receptor 1 (Crhr1) expression decreased in SIS-exposed F0 animals and increased in the TG-F2 and MG-F1 offspring. Expression of enzyme 11-β hydroxysteroid dehydrogenase-2 (11bHSD2) was enhanced in F1 animals. These findings suggest SIS has adverse consequences on the F0 mothers; but their F1–F3 progeny may adapt to this chronic stress; thus supporting the fetal programming hypothesis

Effects of maternal social isolation on adult rodent offspring cognition

Abstract Prenatal experiences can influence offspring physiology and behaviour through the lifespan. Various forms of prenatal stress impair adult learning and memory function and can lead to increased occurrence of anxiety and depression. Clinical work suggests that prenatal stress and maternal depression lead to similar outcomes in children and adolescents, however the long-term effects of maternal depression are less established, particularly in well controlled animal models. Social isolation is common in depressed individuals and during the recent COVID-19 pandemic. Accordingly, for this study we were interested in the effects of maternal stress induced via social isolation on adult offspring cognitive functions including spatial, stimulus–response, and emotional learning and memory that are mediated by different networks centered on the hippocampus, dorsal striatum, and amygdala, respectively. Tasks included a discriminative contextual fear conditioning task and cue-place water task. Pregnant dams in the social isolation group were single housed prior to and throughout gestation. Once offspring reached adulthood the male offspring were trained on a contextual fear conditioning task in which rats were trained to associate one of two contexts with an aversive stimulus and the opposing context remained neutral. Afterwards a cue-place water task was performed during which they were required to navigate to both a visible and invisible platform. Fear conditioning results revealed that the adult offspring of socially isolated mothers, but not controls, were impaired in associating a specific context with a fear-inducing stimulus as assessed by conditioned freezing and avoidance. Results from the water task indicate that adult offspring of mothers that were socially isolated showed place learning deficits but not stimulus-response habit learning on the same task. These cognitive impairments, in the offspring of socially isolated dams, occurred in the absence of maternal elevated stress hormone levels, anxiety, or altered mothering. Some evidence suggested that maternal blood-glucose levels were altered particularly during gestation. Our results provide further support for the idea that learning and memory networks, centered on the amygdala and hippocampus are particularly susceptible to the negative impacts of maternal social isolation and these effects can occur without elevated glucocorticoid levels associated with other forms of prenatal stress