Paternal line multigenerational passage of altered risk assessment behavior in female but not male rat offspring of mothers fed a low protein diet.

Maternal low protein (MLP) diets in pregnancy and lactation impair offspring brain development and modify offspring behavior. We hypothesized multigenerational passage of altered behavioral outcomes as has been demonstrated following other developmental programming challenges. We investigated potential multigenerational effects of MLP in rat pregnancy and/or lactation on offspring risk assessment behavior. Founder generation mothers (F0) ate 20% casein (C) or restricted (R) 10% casein diet, providing four groups: CC, RR, CR, and RC (first letter pregnancy, second letter lactation diet) to evaluate offspring (F1) effects influenced by MLP in F0. On postnatal day (PND 250), F1 males were mated to non-colony siblings producing F2. On PND 90, F2 females (in diestrous) and F2 males were tested in the elevated plus maze (EPM) and open field. Corticosterone was measured at PND 110. Female but not male CR and RC F2 made more entries and spent more time in EPM open arms than CC females. Overall activity was unchanged as observed in male F1 fathers. There were no open field differences in F2 of either sex, indicating that multigenerational MLP effects are due to altered risk assessment, not locomotion. MLP in pregnancy reduced F1 male and F2 female corticosterone. We conclude that MLP in pregnancy and/or lactation increases the innate tendency to explore novel environments in F2 females via the paternal linage, suggesting lower levels of caution and/or higher impulsiveness to explore unknown spaces. Further studies will be necessary to identify the epigenetic modifications in the germ line through the paternal linage.

Pre- and/or postnatal protein restriction developmentally programs affect and risk assessment behaviors in adult male rats.

Developmental programming resulting from a suboptimal intrauterine environment can predispose offspring to a wide-range of lifelong health complications. Little is known about the effects maternal protein restriction during pregnancy and/or lactation has on offspring neurodevelopment. We hypothesized that maternal isocaloric low protein diet during pregnancy and/or lactation would negatively influence male offspring affect and risk assessment behaviors as measured by elevated plus maze and open field tests. Control mothers received 20% casein (C) and restricted mothers (R) 10% casein to provide four groups: CC, RR, CR, and RC (first letter pregnancy diet and second letter lactation diet) to evaluate effects of maternal diet on offspring risk assessment, anxiety and exploratory behaviors. Elevated plus maze results showed an effect of pre- and/or postnatal diet manipulation in open arm time (p<0.05) with increases seen in the RR (157±22.7s), CR (137±23.2s) and RC (146.8±10.8s) offspring relative to CC (52±8.6s) offspring. This behavior indicates decreased avoidance (less anxiety) and increased exploration by experimental groups. However, in the open field test the RR (17±4.2 entries) offspring entered the center zone less than the CC (35±6.6 entries) offspring thus exhibiting increased anxiety with no other groups showing effects. Elevated levels of corticosterone were measured before, during and after immobilization in the RR compared to CC offspring. These findings show protein restriction during critical periods of development negatively program offspring behavior. The underlying anatomical structures affected remain to be elucidated.