Effects of Metabolic Programming on Juvenile Play Behavior and Gene Expression in the Prefrontal Cortex of Rats

Abstract

Early developmental processes, such as metabolic programming, can provide cues to an organism, which allow it to make modifications that are predicted to be beneficial for survival. Similarly, social play has a multifaceted role in promoting survival and fitness of animals. Play is a complex behavior that is greatly influenced by motivational and reward circuits, as well as the energy reserves and metabolism of an organism. This study examined the association between metabolic programming and juvenile play behavior in an effort to further elucidate insight into the consequences that early adaptions have on developmental trajectories. The study also examined changes in expression of four genes (Drd2, IGF1, Opa1, and OxyR) in the prefrontal cortex known to play significant roles in reward, bioenergetics, and social-emotional functioning. Using four distinct variations in developmental programming (high-fat diet, caloric restriction, exercise, or high-fat diet combined with exercise), we found that dietary programming (high-fat diet vs. caloric restriction) had the greatest impact on play behavior and gene expression. However, exercise also induced changes in both measures. This study demonstrates that metabolic programming can alter neural circuits and bioenergetics involved in play behavior, thus providing new insights into mechanisms that allow programming to influence the evolutionary success of an organism.

Tactile stimulation improves cognition, motor, and anxiety‐like behaviors and attenuates the Alzheimer's disease pathology in adult APPNL‐G‐F/NL‐G‐F mice

“…Epigenetic changes in brain have been shown for various behavioral experiences such as modifications in the social environment, including increased licking and grooming of infant rats (Szyf et al., 2008; Weaver et al., 2006). Other epigenetic changes have been shown to be related to stress (e.g., Mychasiuk et al., 2015), diet (Hehar et al., 2016), and mild head injury (Mychasiuk et al., 2015). We are unaware of any studies reporting epigenetic changes with TS from an experimenter although the level of TS delivered by prairie vole parents has been shown to change the expression of genes related to cortical development (Bottom et al., 2020).…”

Peripubertal stress increases play fighting at adolescence and modulates nucleus accumbens CB1 receptor expression and mitochondrial function in the amygdala

“…Given that social play fighting impinges a high metabolic cost to the organism 58 , metabolic differences arising from either early life or through the interaction with stress at puberty might be relevant in this context. In this vein, it is relevant to note that exposure to different metabolic challenges (i.e., high-fat diet, caloric restriction, exercise) during the juvenile period led to drastic changes in play behavior and expression of genes involved in bioenergetics in the brain region (prefrontal cortex) examined 59 . Another study showed that the moderate recurrent hypoglycemia during the pre-weaning period led to abnormal responses to stress and decreases in adolescent social play behavior 60 .…”

Perinatal High-Fat Diet and Bisphenol A: Effects on Behavior and Gene Expression in the Medial Prefrontal Cortex

“…The existing literature presents conflicting evidence of its effect on maternal behavior with both increases and decreases of positive maternal behaviors being reported [24, 25, 26]. In offspring, there are indications of HFD influencing social play, cognitive, and anxiety behaviors [27, 28, 29]. Gestational HFD with 60% fat content has been found to increase pro-inflammatory cytokine expression of IL-1β, microglial activation in the hippocampus of adult male and female offspring [28], and the level of IL-6 in frontal cortex of adult male offspring [30].…”

“…Research on non-human primates also found alterations in the gene expression of serotonin receptors in male and female offspring following maternal HFD [32% fat; 29]. Gestational HFD (60% fat) through P40 is known to affect expression of oxytocin-related genes in the mPFC at P40 [27], and maternal HFD (60% fat) through gestation and lactation also alters opioid and dopamine-related proteins in the mPFC of adult male mice [33]. Few studies have investigated the effect of HFD and BPA on gene expression of hormone receptors in the PFC, despite the interactions of estrogen receptors and inflammation in other brain areas [34].…”