Dietary choline supplementation to dams during pregnancy and lactation mitigates the effects of in utero stress exposure on adult anxiety-related behaviors

Abstract

Brain cholinergic dysfunction is associated with neuropsychiatric illnesses such as depression, anxiety, and schizophrenia. Maternal stress exposure is associated with these same illnesses in adult offspring, yet the relationship between prenatal stress and brain cholinergic function is largely unexplored. Thus, using a rodent model, the current study implemented an intervention aimed at buffering the potential effects of prenatal stress on the developing brain cholinergic system. Specifically, control and stressed dams were fed choline-supplemented or control chow during pregnancy and lactation, and the anxiety-related behaviors of adult offspring were assessed in the open field, elevated zero maze and social interaction tests. In the open field test, choline supplementation significantly increased center investigation in both stressed and nonstressed female offspring, suggesting that choline-supplementation decreases female anxiety-related behavior irrespective of prenatal stress exposure. In the elevated zero maze, prenatal stress increased anxiety-related behaviors of female offspring fed a control diet (normal choline levels). However, prenatal stress failed to increase anxiety-related behaviors in female offspring receiving supplemental choline during gestation and lactation, suggesting that dietary choline supplementation ameliorated the effects of prenatal stress on anxiety-related behaviors. For male rats, neither prenatal stress nor diet impacted anxiety-related behaviors in the open field or elevated zero maze. In contrast, perinatal choline supplementation mitigated prenatal stress-induced social behavioral deficits in males, whereas neither prenatal stress nor choline supplementation influenced female social behaviors. Taken together, these data suggest that perinatal choline supplementation ameliorates the sex-specific effects of prenatal stress.

Sex differences in animal models of schizophrenia shed light on the underlying pathophysiology

“…Therefore males tend to be particularly susceptible to the cognitive impairments associated with prenatal stress exposure. However, female rats show increased anxiety-related behaviour following prenatal stress exposure, which is absent in males (Schulz et al 2014). …”

“…Male-specific locomotor hyperactivity (Bronson et al Male-specific disruption to LI following CORT administration or inescapable foot shock Male rats more affected in object recognition, cued and contextual fear conditioning, and the Female -specific anxiety-related behaviour (Schulz et al 2014). …”

Elevated kynurenine pathway metabolism during neurodevelopment: Implications for brain and behavior

“…Recent studies suggest that early interventions are able to rescue behavioral impairments in adulthood (Nomura et al, 2015; Schulz et al, 2014; Wu et al, 2015). Therefore, early interventions targeting KP enzymes, in particular inhibition of KAT to decrease KYNA levels during critical developmental periods, may attenuate the root cause of long-lasting phenotypic changes, rather than just symptoms in the adult offspring.…”

Maternal Choline Supplementation: A Potential Prenatal Treatment for Down Syndrome and Alzheimer's Disease

“…Numerous studies using rodents demonstrate lasting beneficial effects of increased maternal choline intake during pregnancy on various indices of offspring brain function [71–80]. Specifically, supplementing the maternal diet with additional choline (~4 times higher than found in normal lab chow) enhances memory and spatial cognition in offspring, a benefit that becomes more pronounced with aging [81, 82].…”