Effects of perinatal factors on sirtuin 3, 8-hydroxy-2′- deoxyguanosine, brain-derived neurotrophic factor and serotonin in cord blood and early breast milk: an observational study

Abstract

Background: The profile of sirtuin 3 (SIRT3), 8-hydroxy-2′-deoxyguanosine (8-OHdG), brain-derived neurotrophic factor (BDNF) and serotonin (5-HT) in cord blood and in early breast milk was studied and it was related to perinatal factors. 5-HT and BDNF signalling systems have been claimed to play a critical role in intrauterine development, postnatal adaptation and lactation. Since prematurity and Caesarean birth are frequently associated with inflammation and related oxidative stress, an attempt was made to reveal the adaptive changes of the protective SIRT3 and the complex interplay among these bioactive components in cord blood and early breast milk. Methods: Three groups each consisting of 30 mothers were included in the study: mothers who underwent spontaneous vaginal birth at term (group I), Caesarean section at term (group II) and preterm birth (group III). Venous cord blood and early breast milk samples were collected for measuring the biomarkers. SIRT3, 8-OHdG, BDNF and 5-HT levels were determined by using commercially available ELISA kits. Results: It was demonstrated that cord blood levels of SIRT3, BDNF and 5-HT were markedly reduced whereas those of 8-OHdG were significantly elevated after preterm birth when compared with birth at term. The Caesarean section was associated with a moderate decrease in BDNF and 5-HT, however, both SIRT3 and 8-OHdG remained unaffected. Breast milk levels of all biomarkers studied proved to be independent of their corresponding cord blood concentrations. In response to preterm birth breast milk SIRT3, 8-OHdG and 5-HT increased significantly, while a drastic fall occurred in BDNF. A significant positive relationship was found of 5-HT with SIRT3 and 8-OHdG irrespective of the gestational age and the mode of delivery.

Toll-like receptor 4–mediated enteric glia loss is critical for the development of necrotizing enterocolitis

“…Accordingly, strategies that either directly enhance motility (including the prokinetic agents cisapride and metoclopramide) or restore the function of lost glia (such as the administration of BDNF), or that enhance glia function (as in the Sox10 - Tlr4 ko mouse or the administration of J11) were successful in attenuating NEC. As an unexpected additional proof of concept, breast milk contains BDNF ( 45 ), which might explain the effects of breast milk on increasing gastrointestinal motility ( 46 ) and in preventing NEC ( 47 ).…”

Analysis of Sirtuin 1 and Sirtuin 3 at Enzyme and Protein Levels in Human Breast Milk during the Neonatal Period

“…In this study, we established methods to measure sirtuin 1 and sirtuin 3 enzyme activities both in the cellular pellet and in the aqueous phase of human breast milk. To the best of our knowledge, there is only one study by Nyárády et al that examined certain perinatal factors in relation to the amount of sirtuin 3 protein in native breast milk using an ELISA test [22]. The techniques used were adapted from previous studies by our group in human blood (in vivo) [24] and human cultured cells [46] as well as cultured murine neurons in vitro [18].…”

“…Furthermore, both sirtuin 1 and sirtuin 3 are known to play an important role in oxidative stress and redox signaling [20,21]. During pregnancy and birth, as well as after birth, oxidative stress by reactive oxygen species (ROS) may occur [22,23].…”

“…To the best of our knowledge, little is known about sirtuins in human breast milk. A recent study described the impact of perinatal factors on the amount of sirtuin 3 in early human breast milk; however, the enzymatic activity of sirtuin 3 as a functional parameter was not reported [22].…”

Breastfeeding, pregnancy, medicines, neurodevelopment, and population databases: the information desert

“…Exposure to some prescription medicines in pregnancy, labour and postpartum , may reduce breastfeeding initiation or continuation [ 24 , 46 , 47 ]. The complex physiology of lactation is vulnerable to disruption, particularly by medicines that affect serotoninergic pathways (including antidepressants) [ 48 , 49 ], antagonise prolactin (amphetamines, oestrogens, ergotamine derivatives, aripiprazole, promethazine, possibly diuretics, injected corticosteroids), or reduce oxytocin release (alcohol, opioids, possibly sympathomimetics, anticholinergics, antidepressants) [ 50 – 53 ]. However, we do not know all the reasons underlying the lower breastfeeding rates amongst those using prescription medicines.…”