Maternal Citicoline-Supplemented Diet Improves the Response of the Immature Hippocampus to Perinatal Asphyxia in Rats.

BACKGROUND: Citicoline represents a dietary source of choline, an essential nutrient, and precursor of cell membrane components, highly required during development and post-injury recovery. OBJECTIVES: We previously showed that perinatal asphyxia (PA) induces hippocampal neuroinflammation and injury that are subject to epigenetic change by maternal diet. The present study investigates maternal citicoline-supplemented diet (CSD) impact on offspring hippocampal response to PA. METHODS: Six-day-old Wistar rats from mothers with standard-diet or CSD were exposed to PA. The hippocampal inflammation and injury were assessed by interleukin-1 beta (IL-1b), tumor necrosis factor-alpha (TNFα), and S-100B protein (S-100B), 24-48 h post-asphyxia. The microRNAs species miR124, miR132, miR134, miR146, and miR15a were measured from the hippocampus 24 h post-asphyxia, to investigate its epigenetic response to PA and maternal diet. At maturity, the offspring's behavior was analyzed using open field (OFT), T-maze (TMT), and forced swimming (FST) tests. RESULTS: Our data show that the maternal CSD decreased IL-1b (p = 0.02), TNFα (p = 0.007), and S100B (p = 0.01) at 24 h postexposure, upregulated miR124 (p = 0.03), downregulated miR132 (p = 0.002) and miR134 (p = 0.001), shortened the immobility period in FST (p = 0.01), and increased the percentage of passed trials in TMT (p = 0.01) compared to standard-diet. CONCLUSIONS: Maternal CSD reduces hippocampal inflammation and S100B level, triggers epigenetic changes related to homeostatic synaptic plasticity, memory formation, and neuronal tolerance to asphyxia, decreases the depressive-like behavior, and improves the lucrative memory in offspring subjected to PA. Thus, citicoline could be valuable as a maternal dietary strategy in improving the brain response to PA.

Behavioral and molecular effects of prenatal continuous light exposure in the adult rat.

Disruption of the maternal environment during pregnancy leads to behavioral changes and diseases in the adult offspring. To explore the influence of prenatal continuous light exposure (PCLE) on the adult offspring, we exposed pregnant Wistar rats to constant light during late gestation. Adult PCLE offspring showed an anxiety-like behavior and impairment of short-term memory in different tests. Measurements in the whole brain homogenates from newborn and adult offspring indicated decreased melatonin and serotonin levels and increased reactive oxygen species level in PCLE offspring. Further, we determined melatonin-, serotonin-, oxidative stress-, apoptosis-, and circadian system-related genes expression in different brain areas of adult offspring. The serotonin reuptaker Slc6a4 displayed a decreased expression in the prefrontal cortex of PCLE group. The circadian rhythm-related gene Rora was upregulated in the amygdala of PCLE offspring. Our results point to adverse behavioral effects of PCLE on adult offspring, involving serotonin and melatonin signaling dysregulation, increased chronic oxidative stress, and altered gene expression.