oxytocin and Vitamin-A-Deficiency

A diverse array of data has been associated with autism spectrum disorder (ASD), reflecting the complexity of its pathophysiology as well as its heterogeneity. Two important hubs have emerged, the placenta/prenatal period and the postnatal gut, with alterations in mitochondria functioning crucial in both.. Factors acting to regulate mitochondria functioning in ASD across development are reviewed in this article.. Decreased vitamin A, and its retinoic acid metabolites, lead to a decrease in CD38 and associated changes that underpin a wide array of data on the biological underpinnings of ASD, including decreased oxytocin, with relevance both prenatally and in the gut. Decreased sirtuins, poly-ADP ribose polymerase-driven decreases in nicotinamide adenine dinucleotide (NAD+), hyperserotonemia, decreased monoamine oxidase, alterations in 14-3-3 proteins, microRNA alterations, dysregulated aryl hydrocarbon receptor activity, suboptimal mitochondria functioning, and decreases in the melatonergic pathways are intimately linked to this. Many of the above processes may be modulating, or mediated by, alterations in mitochondria functioning. Other bodies of data associated with ASD may also be incorporated within these basic processes, including how ASD risk factors such as maternal obesity and preeclampsia, as well as more general prenatal stressors, modulate the likelihood of offspring ASD.. Such a mitochondria-focussed integrated model of the pathophysiology of ASD has important preventative and treatment implications.

Topics: ADP-ribosyl Cyclase 1; Autism Spectrum Disorder; Female; Humans; Melatonin; Mitochondria; Oxytocin; Placenta; Pregnancy; Serotonin; Vitamin A; Vitamin A Deficiency

Vitamin A (VA) is an essential nutrient for the development of the brain. We previously found that children with autism spectrum disorder (ASD) have a significant rate of VA deficiency (VAD). In the current study, we aim to determine whether VAD is a risk factor for the generation of autistic-like behaviors via the transcription factor retinoic acid receptor beta (RARβ)-regulated cluster of differentiation 38 (CD38)-oxytocin (OXT) axis.. Gestational VAD or VA supplementation (VAS) rat models are established, and the autistic-like behaviors in the offspring rats are investigated. The different expression levels of RARβ and CD38 in hypothalamic tissue and serum retinol and OXT concentration are tested. Primary cultured rat hypothalamic neurons are treated with all-trans retinoic acid (atRA), and recombinant adenoviruses carrying the rat RARβ (AdRARβ) or RNA interference virus RARβ-siRNA (siRARβ) are used to infect neurons to change RARβ signal. Western blotting, chromatin immunoprecipitation (ChIP), and intracellular Ca. Gestational VAD might be a risk factor for autistic-like behaviors due to the RARβ signal suppression of CD38 expression in the hypothalamus of the offspring, which improves with VAS during the early-life period. The nutritional status during pregnancy and the early-life period is important in rats.

Topics: ADP-ribosyl Cyclase; ADP-ribosyl Cyclase 1; Animals; Anxiety; Autistic Disorder; Depression; Hypothalamus; Interpersonal Relations; Membrane Glycoproteins; Oxytocin; Rats; Rats, Sprague-Dawley; Receptors, Retinoic Acid; Vitamin A; Vitamin A Deficiency