Ancestral Exposure to Stress Generates New Behavioral Traits and a Functional Hemispheric Dominance Shift

Abstract

In a continuously stressful environment, the effects of recurrent prenatal stress (PS) accumulate across generations and generate new behavioral traits in the absence of genetic variation. Here, we investigated if PS or multigenerational PS across 4 generations differentially affect behavioral traits, laterality, and hemispheric dominance in male and female rats. Using skilled reaching and skilled walking tasks, 3 findings support the formation of new behavioral traits and shifted laterality by multigenerational stress. First, while PS in the F1 generation did not alter paw preference, multigenerational stress in the F4 generation shifted paw preference to favor left-handedness only in males. Second, multigenerational stress impaired skilled reaching and skilled walking movement abilities in males, while improving these abilities in females beyond the levels of controls. Third, the shift toward left-handedness in multigenerationally stressed males was accompanied by increased dendritic complexity and greater spine density in the right parietal cortex. Thus, cumulative multigenerational stress generates sexually dimorphic left-handedness and dominance shift toward the right hemisphere in males. These findings explain the origins of apparently heritable behavioral traits and handedness in the absence of DNA sequence variations while proposing epigenetic mechanisms.

Proximate causes and consequences of intergenerational influences of salient sensory experience

“…It is not uncommon to observe sex‐differences in the effects of intergenerational influences of salient parental environments. Exposing parental rodents to stressors as well as dietary manipulations have been shown to affect one sex and not the other depending not only on the parental perturbation but also the task on which the offspring are tested . Therefore, once again, our data agree with the existing literature that male and female offspring may shoulder the legacy of parental stress differently and attention needs to be paid to the parental environmental experience and the dependent variable being tested in the offspring.…”

Lineage- and Sex-Dependent Behavioral and Biochemical Transgenerational Consequences of Developmental Exposure to Lead, Prenatal Stress, and Combined Lead and Prenatal Stress in Mice

“…Based on an absolute gray volume index, F3 females also exhibited reductions in both cortical and hippocampal neuronal density. In a comparison of paw use as a measure of brain laterality, multigenerationally exposed, but not transgenerationally exposed, F4 males exhibited increases in left paw preference, indicative of altered brain laterality (Ambeskovic et al 2017).…”

Environmental Intervention as a Therapy for Adverse Programming by Ancestral Stress

“…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. The understanding that stress is mainly uncontrollable and transferred to filial generations highlights the need to identify interventions that can treat the adverse effects of programming by ancestral stress.…”