Abstract
Epigenetic mechanisms such as DNA methylation elicit lasting changes in gene expression and likely mediate gene–environment interactions that shape brain development, behavior, and emotional health. Myriad environmental factors influence DNA methylation, including methyl donor content in the paternal diet, could influence methylation in offspring via changes in the paternal germ line. The present study examines the effects of paternal methyl donor dietary deficiency on offspring’s emotional behaviors, including anxiety, social interaction, and depression-like behavior. We previously found that rats bred to display high levels of anxiety- and depression-like behavior exhibit diminished DNA methylation in the amygdala. We also observed that depleting dietary methyl donor content exacerbated the rats’ already high levels of anxiety- and depression-like behavior. Here we sought to determine whether paternal dietary methyl donor depletion elicits intergenerational effects on first generation (F1) offspring’s behavior (potentially triggering a similar increase in anxiety- and/or depression-like behavior). Thus, adult male rats prone to high anxiety/depression-like behavior, were fed either a methyl donor depleted (DEP) or control (CON) diet for 5 weeks prior to mating. They were paired with females and resultant F1 male offspring were subjected to a behavioral test battery in adulthood. F1-DEP offspring showed a similar behavioral profile to the F0 males, including greater depression-like behavior in the forced swim test (FST) and increased anxiety-like behavior in the open field test (OFT). Future work will interrogate molecular changes in the brains of F1 offspring that mediate these intergenerational effects of paternal methyl donor dietary content on offspring emotional behavior.
Highlights
Epigenetic mechanisms lie at the crossroads where ‘nature’ meets ‘nurture’ and likely mediate gene–environment interactions that shape neurodevelopment, behavior, and neuropsychological health [1]
Because our prior experiments found that manipulating dietary methyl donor content was effective in shifting adult low novelty responder rat (LR) rats’ behavioral phenotype [16], the present study focussed on potential intergenerational effects of paternal methyl donor depletion on LR offspring only
When first generation (F1)-CON and F1-DEP male LR offspring reach adulthood, they were evaluated in an emotional behavioral test battery
Summary
Epigenetic mechanisms lie at the crossroads where ‘nature’ meets ‘nurture’ and likely mediate gene–environment interactions that shape neurodevelopment, behavior, and neuropsychological health [1]. DNA methyltransferase (DNMT) enzymes transfer methyl groups from S-adenosylmethionine (SAM) to cytosine [10], so diets lacking folate or other methyl donors can impede SAM synthesis, thereby leading to DNA hypomethylation [11,12,13]. Depleting dietary methyl donor content in adult animals decreases DNA methylation markers in the brain [13], c 2018 The Author(s).
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