Lifespan Psychomotor Behaviour Profiles of Multigenerational Prenatal Stress and Artificial Food Dye Effects in Rats

Abstract

The 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.

Environmental Intervention as a Therapy for Adverse Programming by Ancestral Stress

“…Female rats were isolated starting at the age of 90 days until parturition, thus withdrawing the benefit of social interaction and generating both physiological and behavioural changes. The stress severity was comparable, yet different in nature, to an established semi-random restraint and swim stress procedure used in earlier transgenerational studies629. TPS and MPS both reduced total hippocampal GR density, which resembles changes commonly seen after prenatal stress43031.…”

“…Prenatal programming of the developing brain and HPA axis has consequences that extend into adulthood, which may result in altered motor activity24642. The present study examined animals at the age of 30, 60 and 90 days, thus covering the main stages of adolescent development.…”

“…More recently, early life stress was shown to not only influence the F1 offspring, but also future filial generations. Transgenerational programming by stress was shown to alter affective state and sensorimotor behaviour6, endocrine functions7 and heritable changes in DNA methylation status and microRNA (miRNA) expression89. Moreover, cumulative multigenerational stress has recently been shown to generate new behavioural traits in a sexually dimorphic manner10.…”

“…To determine the impact of EE on transgenerational versus cumulative ancestral stress, the design used (1) a lineage of transgenerational prenatal stress in which the parental generation but not the F1-F3 generations experienced stress, and (2) a lineage of multigenerational prenatal stress, in which each the parental and the offspring generations experienced gestational stress682425. The F3 generation is of particular relevance because it is the first generation in the maternal lineage that is not directly exposed to prenatal stress and therefore changes may be considered programmed through epigenetic inheritance26.…”

Multigenerational prenatal stress increases the coherence of brain signaling among cortico–striatal–limbic circuits in adult rats

“…Our previous work showed that http multi-generational experience of recurrent PNS accumulates across generations and sensorimotor impairments in later generations exceed the effects of PNS in the first generation (Erikson et al, 2014;Yao et al, 2014). Contrary to such sensorimotor deficits, we propose that some essential cognitive functions may reveal adaptive changes of stress coping in multi-generational prenatal stressed (MGPNS) rats.…”