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

Abstract

<b><i>Background:</i></b> Citicoline represents a dietary source of choline, an essential nutrient, and precursor of cell membrane components, highly required during development and post-injury recovery. <b><i>Objectives:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> Our data show that the maternal CSD decreased IL-1b (<i>p</i> = 0.02), TNFα (<i>p</i> = 0.007), and S100B (<i>p</i> = 0.01) at 24 h postexposure, upregulated miR124 (<i>p</i> = 0.03), downregulated miR132 (<i>p</i> = 0.002) and miR134 (<i>p</i> = 0.001), shortened the immobility period in FST (<i>p</i> = 0.01), and increased the percentage of passed trials in TMT (<i>p</i> = 0.01) compared to standard-diet. <b><i>Conclusions:</i></b> 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.

A Scoping Review of Rodent Studies Investigating the Epigenetic Mechanisms in the Brain Underlying the Effects of Diet on Depressive-like Behaviour

“…Similarly, two studies investigated the effects of calories in the diet, including a hypercaloric diet or a calorie-restricted diet [ 22 , 27 ]. Lastly, two studies investigated the effects of supplementation or depletion of methyl donors in the diet such as choline [ 24 , 29 ].…”

Does a Single Exposure to General Anesthesia Have a Cumulative Effect on the Developing Brain after Mild Perinatal Asphyxia?

“…The asphyxia exposure was performed at PND6 in a flow-through chamber system and consisted of a 90-min exposure to either normoxia or asphyxia using a hypoxic-hypercapnic gas mixture (9% O 2 , 20% CO 2 in N 2 ) at a constant rate of 2 L/min using an open non-rebreathing system. This model of PA was developed by Helmy et al [ 17 ] and modified and previously used by us in several studies [ 16 , 18 ]. During the asphyxia episode, the ambient temperature was controlled using a heating pad to maintain the body temperature of the pups at 36.6 °C.…”

“…The accommodation trial consisted in placing the rat in the cylinder containing water at 25 °C at a depth of 6 cm for 7 min. After 24 h, the rats were tested by placing them in the same cylinder containing water at a depth of 18 cm for 5 min, in order not to touch the bottom of the cylinder with the posterior legs [ 16 ]. The FST is based on the evaluation of rats exposed to water.…”

“…PA increases hippocampal inflammation and injury, making this structure a reference point in the study of potential neurodevelopmental risks associated with pediatric anesthesia [ 16 ].…”

Epigenetics in inflammatory liver diseases: A clinical perspective (Review)

“…Since miRNA represents epigenetic markers that modulate terminal cell differentiation and developmental changes, there has been great interest in achieving new miRNA-targeted epigenetic therapies and identifying new epigenetic markers for various clinical paradigms ( 17 ). At present, there are numerous miRNA species recognized, being independently and organ-specifically coded which can modulate the protein synthesis and function in health and disease.…”